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1
Kuznetsov, Aleksei, and Jaak Järv. "Ligand structure controlled allostery in cAMP-dependent protein kinase catalytic subunit." Open Life Sciences 4, no. 2 (June 1, 2009): 131–41. http://dx.doi.org/10.2478/s11535-009-0012-6.
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AbstractProtein kinase A (cAMP dependent protein kinase catalytic subunit, EC 2.7.11.11) binds simultaneously ATP and a phosphorylatable peptide. These structurally dissimilar allosteric ligands influence the binding effectiveness of each other. The same situation is observed with substrate congeners, which reversibly inhibit the enzyme. In this review these allosteric effects are quantified using the interaction factor, which compares binding effectiveness of ligands with the free enzyme and the pre-loaded enzyme complex containing another ligand. This analysis revealed that the allosteric effect depends upon structure of the interacting ligands, and the principle “better binding: stronger allostery” observed can be formalized in terms of linear free-energy relationships, which point to similar mechanism of the allosteric interaction between the enzyme-bound substrates and/or inhibitor molecules. On the other hand, the type of effect is governed by ligand binding effectiveness and can be inverted from positive allostery to negative allostery if we move from effectively binding ligands to badly binding compounds. Thus the outcome of the allostery in this monomeric enzyme is the same as defined by classical theories for multimeric enzymes: making the enzyme response more efficient if appropriate ligands bind.
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Merugu, Ramchander, Uttam Kumar Neerudu, Karunakar Dasa, and Kalpana V. Singh. "Molecular docking studies of deacetylbisacodyl with intestinal sucrase-maltase enzyme." International Journal of Advances in Scientific Research 2, no. 12 (January 1, 2017): 191. http://dx.doi.org/10.7439/ijasr.v2i12.3821.
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Molecular docking of sucrase-isomaltase with ligand deacetylbisacodyl when subjected to docking analysis using docking server, predicted in-silico result with a free energy of -3.36 Kcal/mol which was agreed well with physiological range for protein-ligand interaction, making bisacodyl probable potent anti-isomaltase molecule. According to docking server Inhibition constant is 5.98Mm. which predicts that the ligand is going to inhibits enzyme and result in a clinically relevant drug interaction with a substrate for the enzyme. Hydrogen bond with bond length 3.45is formed between Pro 64 (A) of target and of ligand, which is again indicative of the docking between target and ligand. Excellent electrostatic interactions of polar, hydrophobic, pi-pi and Van der walls are observed. The proteinligand interaction study showed 6 amino acid residues interaction with the ligand.
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Mulyati, Budi, and Riong Seulina Panjaitan. "Studi Penambatan Molekul Flavonoid Pada Reseptor α-Glukosidase menggunakan PLANTS." JURNAL KIMIA MULAWARMAN 18, no. 2 (May 30, 2021): 68. http://dx.doi.org/10.30872/jkm.v18i2.1004.
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ABSTRACT
Plants that contain flavonoids are widely used in traditional medicine. Flavonoids can reduce blood glucose levels with their ability as anti-oxidants. The purpose of this study was to determine natural compounds from flavonoid derivatives that have good affinity and conformation and their interactions in inhibiting α-glucosidase (an enzyme that breaks down carbohydrates into glucose) and determine the sequence of ligands that interact more strongly with α protein / enzyme α-glucosidase. Molecular docking is a computational method that aims to imitate the interaction of a ligand molecule with the protein it targets in in-vitro tests. Molecular docking between flavonoids and α-glucosidase receptors was carried out using the PLANTS method to see its affinity. The flavonoids used as ligands were flavones, flavanols and chalcone with the results of the docking scores respectively, -65.41, -64.39 and -63.07 where the standard ligand used in this study was deoxynojirimycin (-77.12). In the active side of the α-Glucosidase enzyme that binds to flavonoid ligands is Gly 555, Glu 526 and Pro 556.
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BOUGIE, Isabelle, Amélie PARENT, and Martin BISAILLON. "Thermodynamics of ligand binding by the yeast mRNA-capping enzyme reveals different modes of binding." Biochemical Journal 384, no. 2 (November 23, 2004): 411–20. http://dx.doi.org/10.1042/bj20041112.
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RNA-capping enzymes are involved in the synthesis of the cap structure found at the 5′-end of eukaryotic mRNAs. The present study reports a detailed study on the thermodynamic parameters involved in the interaction of an RNA-capping enzyme with its ligands. Analysis of the interaction of the Saccharomyces cerevisiae RNA-capping enzyme (Ceg1) with GTP, RNA and manganese ions revealed significant differences between the binding forces that drive the interaction of the enzyme with its RNA and GTP substrates. Our thermodynamic analyses indicate that the initial association of GTP with the Ceg1 protein is driven by a favourable enthalpy change (ΔH=−80.9 kJ/mol), but is also clearly associated with an unfavourable entropy change (TΔS=−62.9 kJ/mol). However, the interaction between Ceg1 and RNA revealed a completely different mode of binding, where binding to RNA is clearly dominated by a favourable entropic effect (TΔS=20.5 kJ/mol), with a minor contribution from a favourable enthalpy change (ΔH=−5.3 kJ/mol). Fluorescence spectroscopy also allowed us to evaluate the initial binding of GTP to such an enzyme, thereby separating the GTP binding step from the concomitant metal-dependent hydrolysis of GTP that results in the formation of a covalent GMP–protein intermediate. In addition to the determination of the energetics of ligand binding, our study leads to a better understanding of the molecular basis of substrate recognition by RNA-capping enzymes.
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HOWES, Barry D., Nigel C. VEITCH, Andrew T. SMITH, Christopher G. WHITE, and Giulietta SMULEVICH. "Haem-linked interactions in horseradish peroxidase revealed by spectroscopic analysis of the Phe-221→Met mutant." Biochemical Journal 353, no. 2 (January 8, 2001): 181–91. http://dx.doi.org/10.1042/bj3530181.
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A gene encoding a Phe-221-to-Met substitution in the haem enzyme horseradish peroxidase has been constructed and expressed in Escherichia coli. In the wild-type enzyme the side chain of Phe-221 is tightly stacked against the imidazole ring of His-170, which provides the only axial ligand to the haem iron atom. The Phe-221 → Met enzyme is active, and forms characteristic complexes with typical peroxidase ligands (CO, cyanide, fluoride), and with benzhydroxamic acid. Significant differences between the mutant and wild-type enzymes can be detected spectroscopically. These include a change in the Fe(III) resting state of the enzyme to an unusual quantum mechanically mixed-spin haem species, a marked decrease in the pKa of the alkaline transition and a reduction in enzyme stability at alkaline pH for both Fe(III) and Fe(II) forms. The perturbation of the haem pocket in the mutant can be attributed to several factors, including the increased steric freedom and solvent accessibility of the His-170 ligand, as indicated by 1H-NMR data, and the loss of the πŐπ interaction between His-170 and Phe-221.
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Tharuni, Boya, T. Sathish, G. Nadana Raja Vadivu, and K. Vasumathi. "IN SILICO ANALYSIS OF DELTA 6 DESATURASE - A KEY ENZYME FOR OMEGA €“3/6€“ FATTY ACID PRODUCTION." International Journal of Advanced Research 9, no. 02 (February 28, 2021): 818–23. http://dx.doi.org/10.21474/ijar01/12519.
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Delta 6 desaturase is a key enzyme involved in the production of omega 3/6 fatty acids and it is the rate-limiting step. The study aims to characterize the delta 6 desaturase enzyme and to find the binding affinity of various ligand with the protein by docking. It is found that delta 6 desaturase enzyme sequence is very unique and has less similarity with the other desaturase protein. The structural analysis was performed by Ramachandran plot and SCOPe structure prediction. Modeller is used to determine the DOPE score of the selected enzyme. The lowest DOPE score protein is chosen to determine the binding affinity of ligand molecules. Three different ligands were selected and its interaction was determined by the PyRX - Autodock Vina. These studies will give a better idea of the interaction of various molecules, which help to deduce its function by further experimentation.
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Veniere, Sylvie, Christophe Ampe, Joël Vandekerckhove, and Anja Lambrechts. "The Interaction of Proline-Rich Ligands with Profilin Probed with an Enzyme-Linked Immunosorbent Assay." Journal of Biomolecular Screening 14, no. 4 (April 2009): 350–59. http://dx.doi.org/10.1177/1087057109332594.
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To detect interactions of different proline-rich ligands with profilins, the authors developed a simple analytical antibody-based screening method. Profilin I or profilin IIa was coated in microplates, and ligand binding was monitored via antibody detection. Using purified components, the authors show that the assay is very sensitive as nanomolar concentrations of recombinant profilin ligands can be used. They further apply this technique to detect interaction of profilin with various proline-rich partners, either endogenously present or ectopically expressed as tagged fusions, using lysates. With this assay, the authors identify Shootin1 as a novel profilin IIa partner. In addition, they demonstrate that this assay can be used for studying competition or ternary complex formation. In conclusion, they developed a sensitive, easy-to-use, and versatile method for the study of the interaction between profilin and different ligands. ( Journal of Biomolecular Screening 2009:350-359)
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SYGUSCH, Jurgen, and Danielle BEAUDRY. "Subunit interaction in mammalian aldolases." Biochemical Journal 323, no. 3 (May 1, 1997): 671–76. http://dx.doi.org/10.1042/bj3230671.
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Enzyme inactivation was utilized to study subunit interaction in the homotetrameric glycolytic enzyme, aldolase. Isoenzymes from rabbit liver and skeletal muscle were inactivated in the presence of Pi and d-glyceraldehyde-P to a maximum stoichiometry of one modification per aldolase subunit. Subunit modification increased net negative charge on each subunit surface and was used to resolve modified aldolase isoenzymes into various chromatographic species. A combination of anion-(Mono Q) and cation- (Mono S) exchange chromatography separated the modified aldolase homotetramers into three distinct enzyme populations: unchanged enzyme, fully modified enzyme corresponding to one ligand molecule incorporated per subunit and partially modified enzyme in which only one subunit out of four is modified. Both fully and partially modified species were devoid of catalytic activity. Activity loss through modification of a single subunit in both aldolase isoenzymes indicates tightly coupled communication between subunit active sites and suggests simple functional regulation of aldolases.
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Aziz, Fitri Kusvila, Cantika Nukitasari, Fauziyah Ardli Oktavianingrum, Lita Windy Aryati, and Broto Santoso. "Hasil In Silico Senyawa Z12501572, Z00321025, SCB5631028 dan SCB13970547 dibandingkan Turunan Zerumbon terhadap Human Liver Glycogen Phosphorylase (1l5Q) sebagai Antidiabetes." Jurnal Kimia VALENSI 2, no. 2 (November 30, 2016): 120–24. http://dx.doi.org/10.15408/jkv.v2i2.4170.
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Abstrak Human Liver Glycogen Phosphorylase (HLGP), suatu katalis glikogen yang mengontrol pelepasan glukosa-1-fosfat glikogen dari hati. Enzim ini mempunyai peran sentral dalam luaran glukosa hati sehingga menjadi target obat antidiabetik. Kajian docking dilakukan pada komputer dengan prosesor Intel Pentium, RAM 1 GB dan Windows 7. Ligan yang digunakan adalah senyawa obat (Z12501572, Z00321025, SCB5631028 dan SCB13970547), dataset pembanding aktif glycogen phosphorylase outer dimer site (PYGL-out) dan decoysdari www.dekois.com dan turunan zerumbon. Protein dipisahkan dari ligan nativ dan semua ligan beserta protein dikonversi menggunakan PyRx. Visualisasi interaksi ligan-protein dihasilkan dengan program Protein-Ligand Interaction Profiler (PLIP) dan PyMOL. Senyawa ZER11 memiliki binding energy terbaik, yaitu -7.11 kkal/mol (untuk metode LGA dan GA) dan -4.08 kkal/mol untuk metode SA. Nilai binding energy tersebut lebih rendah dari pada nilai untuk ligan native dan satu dari keempat senyawa obat, terlebih jika dibandingkan dengan bindingaffinity dari dataset dan decoys. Interaksi ligan-protein pada ketiga metode tersebut ditemukan sangat bervariasi. Hal berbeda terjadi untuk metode Vina, bindingenergy ZER11 (-9.9 kkal/mol) lebih baik dibandingkan dengan ligan native dan keempat senyawa obat. Senyawa ZER11 memiliki residu interaksi yang sama dengan ligan native pada TRP67 dan LYS191 untuk metode Vina. Kata kunci: PDBID-1L5Q, AutoDock, docking molekuler, vina, antidiabetes Abstract Human Liver Glycogen Phosphorylase (HLGP) can catalyze glycogen and control the release of glucose-1-phosphate of glycogen from the liver. This enzyme has a central role in output rule of liver glucose as it can be used as an antidiabetic drug targets. Docking studies were carried out on PC with Intel Pentium, 1 GB RAM, in environment of Windows 7. Ligands used are drug compounds (Z12501572, Z00321025, SCB5631028 and SCB13970547), the active dataset comparator wasglycogenphosphorylase outer dimer site (PYGL-out) and decoys from www.dekois.com andzerumbonederivates. Protein was separated from its native ligand and all ligands including the protein were converted to pdbqt using PyRx. The interaction of protein-ligand was visualized using software of PLIP and PyMOL. Compound of ZER11 had the best binding energy were -7.11 kcal/mol (LGA and GA) and -4.08 kcal/mol (SA). The binding energy value was lower than the ligand native and one of the four drug compounds, especially compared with the binding affinity of dataset and decoys. Vice versa, for Vina method, the value of ligand binding protein for ZER11 (-9.9 kcal/mol) was better than the ligand native and all of the fourth drugcompounds. Vina result showed that ZER11 had the same residual interaction as the ligand native, which are TRP67 and LYS191. Keyword: PDBID-1L5Q, AutoDock, molecular docking, vina, antidiabetic DOI: http://dx.doi.org/10.15408/jkv.v0i0.4170
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Vadivelu, Annapoorna. "Molecular docking studies of 1,3,4 -thiadiazoles as myeloperoxidase inhibitors." Journal of Pharmaceutical and Biological Sciences 9, no. 1 (July 15, 2021): 63–69. http://dx.doi.org/10.18231/j.jpbs.2021.008.
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Myeloperoxidase (MPO) is a heterodimeric, cationic and glycosylated haeme enzyme which gets released under increased oxidative stress producing neutrophil oxidant, hypochlorous acid having the capacity to modify various biomolecules by chlorination and/or oxidation of sulfhydryl groups in proteins causing their inactivation and promoting inflammatory tissue damage. Different levels of hypochlorus acid are used as a trait marker for prescribing the disorders e.g. atherosclerosis, rheumatoid arthritis, lung cancer, Immuno-reactivity. Mini library of 22500 2,5disubstituted 1,3,4 thiadiazoles were docked with Myeloperoxidase in order to identify the potent inhibitor against the enzyme. The chemical nature of the protein and ligands greatly influence the performance of docking process. Keeping this fact in view, critical evaluation of the performance was performed by GLIDE by HTVS, SP and XP. The ADME parameters by QIKPROP and protein-ligand binding free energies were calculated using the Prime/MM-GBSA module of Schrödinger.Both hydrogen bonding and hydrophobic interactions contributed significantly for its ligand binding and core influence the target site through prominent hydrophobic and charged interaction with the backbone and side chain residues in the target site that improves the affinity of the molecule. The compound selected as potent inhibitor is having minimum binding affinity, maximum GScore and minimum FlexX energy. The amino acids residues ASP98, ASP94, THR100 and GLU 102 in the MPO gene domain active site form hydrogen bonds with the ligand. Compounds 3350-5150 showed better interaction with haeme enzyme for further understanding of structures, reliability and Biomolecularactivityy in connection with oxidative stress induced disorders.
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Scior, Thomas R. F., and Israel Quiroga. "Induced fit for cytochrome P450 3A4 based on molecular dynamics." ADMET and DMPK 7, no. 4 (December 10, 2019): 252–66. http://dx.doi.org/10.5599/admet.729.
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The present study aims at numerically describing to what extent substrate - enzyme complexes in solution may change over time as a natural process of conformational changes for a liganded enzyme in comparison to those movements which occur independently from substrate interaction, i.e. without a ligand. To this end, we selected structurally known pairs of liganded / unliganded CYP450 3A4 enzymes with different geometries hinting at induced fit events. We carried out molecular dynamics simulations (MD) comparing the trajectories in a “cross-over†protocol: (i) we added the ligand to the unliganded crystal form which should adopt geometries similar to the known geometry of the liganded crystal structure during MD, and – conversely – (ii) we removed the bound ligand form the known liganded complex to test if a geometry similar to the known unliganded (apo-) form can be adopted during MD. To compare continues changes we measured root means square deviations and frequencies. Results for case (i) hint at larger conformational changes required for accepting the substrate during its approach to final position – in contrast to case (ii) when mobility is fairly reduced by ligand binding (strain energy). In conclusion, a larger conformational sampling prior to ligand binding and the freezing-in (rigidity) of conformations for bound ligands can be interpreted as two conditions linked to induced-fit.
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Agoni, Clement, Pritika Ramharack, and Mahmoud E. S. Soliman. "Synergistic Interplay of The Co-administration of Rifampin And Newly Developed Anti-TB Drug: Could It Be a Promising New Line of TB Therapy?" Combinatorial Chemistry & High Throughput Screening 21, no. 6 (August 27, 2018): 453–60. http://dx.doi.org/10.2174/1386207321666180716093617.
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Background: Rifampin resistance has dampened the existing efforts being made to control the global crisis of Tuberculosis and antimicrobial resistance in general. Previous studies that attempted to provide insights into the structural mechanism of Rifampin resistance did not utilize the X-ray crystal structure of Mycobacterium tuberculosis RNA polymerase due to its unavailability. Methods/Results: We provide an atomistic mechanism of Rifampin resistance in a single active site mutating Mycobacterium tuberculosis RNA polymerase, using a recently resolved crystal structure. We also unravel the structural interplay of this mutation upon co-binding of Rifampin with a novel inhibitor, D-AAP1. Mutation distorted the overall conformational landscape of Mycobacterium tuberculosis RNA polymerase, reduced binding affinity of Rifampin and shifted the overall residue interaction network of the enzyme upon binding of only Rifampin. Interestingly, co-binding with DAAP1, though impacted by the mutation, exhibited improved Rifampin binding interactions amidst a distorted residue interaction network. Conclusion: Findings offer vital conformational dynamics and structural mechanisms of mutant enzyme-single ligand and mutant enzyme-dual ligand interactions which could potentially shift the current therapeutic protocol of Tuberculosis infections.
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Dikant, F., F. Gáplovský, and V. Garaj. "Virtual screening of combinatorial library of novel benzenesulfonamides on mycobacterial carbonic anhydrase II." European Pharmaceutical Journal 63, no. 2 (December 1, 2016): 1–6. http://dx.doi.org/10.1515/afpuc-2016-0020.
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AbstractCombinatorial library of novel benzenesulfonamides was docked (Schrodinger Glide) into mycobacterial carbonic anhydrase (mtCA II) and human (hCA II) isoforms with an aim to find drug candidates with selective activity on mtCA II. The predicted selectivity was calculated based on optimized MM-GBSA free energies for ligand enzyme interactions. Selectivity, LogP (o/w) and interaction energy were used to calculate the selection index which determined the subset of best scoring molecules selected for further evaluation. Structure-activity relationship was found for fragment subsets, showing us the possible way regarding how to influence lipophilicity without affecting ligand-enzyme binding properties.
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İş, Yusuf Serhat. "Elucidation of Ligand/Protein Interactions between BCR-ABL Tyrosine Kinase and Some Commercial Anticancer Drugs Via DFT Methods." Journal of Computational Biophysics and Chemistry 20, no. 04 (June 2021): 433–47. http://dx.doi.org/10.1142/s273741652150023x.
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In this study, the interactions of 7 commercially available BCR-ABL tyrosine kinase enzyme inhibitors with amino acids in the active site of the relevant enzyme were investigated quantum mechanically. Here a per-residue study was carried out. Interaction energies were calculated by using the coordinates of the critical residues in the binding site of the enzyme and the drug molecules docked in this region. DFT methods were used during the QM processes. All interaction energies were calculated via M06-2X functional and 6-31G (d,p) basis set in vacuum. Based on the results obtained, it was tried to be determined which of the important residues in the binding cavity of the enzyme could better interact with the examined ligands. It is thought that this study may contribute to the development of tyrosine kinase enzyme inhibitors.
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Abdi, Sayed Aliul Hasan, Abdulaziz Alzahrani, Saleh Alghamdi, Ali Alquraini, and Adel Alghamdi. "Hexaconazole exposure ravages biosynthesis pathway of steroid hormones: revealed by molecular dynamics and interaction." Toxicology Research 11, no. 1 (December 16, 2021): 60–76. http://dx.doi.org/10.1093/toxres/tfab113.
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Abstract Widespread application of hexaconazole for agriculture purpose poses a threat to human health by disrupting normal endocrine homeostasis. To avoid adverse health effects on human, it is crucial to identify the effects of hexaconazole on key enzymes responsible for steroidal hormone synthesis. In view of this, present study was conducted to investigate the interaction mechanisms of hexaconazole with key enzymes in comparison with their food drug administration (FDA) approved inhibitor by molecular docking and molecular dynamics simulations. Results indicate that hexaconazole contacts with the active site of the key enzymes required for steroidal hormonal synthesis. Results pertaining to root-mean-square deviation, root-mean-square calculation, radius of gyration, hydrogen bonding and solvent accessible surface area exhibited that the interaction pattern and stability of interaction of hexaconazole was similar to enzyme specific inhibitor. In addition, ligand and enzyme complex interaction energy of hexaconazole was almost similar to key enzyme and FDA-approved enzyme specific inhibitor complex. This study offers a molecular level of understanding of hexaconazole with different enzymes required for steroidal hormonal synthesis. Findings of the study clearly suggest that hexaconazole has efficacy to stably interact with various enzyme required to progress the pathway of hormonal synthesis. If incessant exposure of hexaconazole occurs during agricultural work it may lead to ravage hormonal synthesis or potent endocrine disruption. The result of binding energy and complex interaction energy is depicted in the graphical abstract.
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Oktaviani, Annisa Rizqi Dwi, Veronica Shania Aprillia, Eko Suhartono, and Noer Komari. "Hesperidin Interaction with HMG-CoA-Reductase Enzyme in Hypercholesterolemia: A Study in Silico." Berkala Kedokteran 17, no. 2 (September 29, 2021): 173. http://dx.doi.org/10.20527/jbk.v17i2.11692.
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Abstract: Dyslipidemia is a degenerative disease occurred with increased levels of fat and cholesterol levels in blood. One of the proteins used as anti-cholesterol is an HMG-CoA-Reductase. Hesperidin in orange peel can reduce cholesterol levels by interacting with HMG-CoA-Reductase. To prove this, an in silico method was used by using swissdock.ch (http://swissdock.ch/docking#). The receptor protein in dyslipidemia was obtained from the RCSB Protein Data Bank (https://www.rcsb.org) namely HMG-CoA-reductase receptor with code PDB: 1HW9. The natural ligand, hesperidin, was obtained from PubChem with code: 10621 (https://pubchem.ncbi.nlm.nih.gov/). Protein was prepared by omitting the natural ligand residues present in the protein. Ligand and protein preparations were used by the chimera 1.15. The result of this study indicated that the interaction of hesperidin with several amino acid recidues was predicted to provide inhibitory activity on HMG-CoA reductase as the protein target. Inhibition of HMG-CoA reductase will reduce mevalonate synthesis so that cholesterol levels will decrease. Keywords: hesperidin, HMG-CoA-Reductase, cholesterol, dyslhahipidemia
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Kashaw, Sushil K., Shivangi Agarwal, Mitali Mishra, Samaresh Sau, and Arun K. Iyer. "Molecular Docking Analysis of Caspase-3 Activators as Potential Anticancer Agents." Current Computer-Aided Drug Design 15, no. 1 (December 14, 2018): 55–66. http://dx.doi.org/10.2174/1573409914666181015150731.
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Introduction: Caspase-3 plays a leading role in apoptosis and on activation, it cleaves many protein substrates in cells and causes cell death. Since many chemotherapeutics are known to induce apoptosis in cancer cells, promotion or activation of apoptosis via targeting apoptosis regulators has been suggested as a promising strategy for anticancer drug discovery. In this paper, we studied the interaction of 1,2,4-Oxadiazoles derivatives with anticancer drug target enzymes (PDB ID 3SRC). Methods: Molecular docking studies were performed on a series of 1,2,4-Oxadiazoles derivatives to find out molecular arrangement and spatial requirements for their binding potential for caspase-3 enzyme agonistic affinity to treat cancer. The Autodock 4.2 and GOLD 5.2 molecular modeling suites were used for the molecular docking analysis to provide information regarding important drug receptor interaction. Results and Conclusion: Both suites explained the spatial disposition of the drug with the active amino acid in the ligand binding domain of the enzyme. The amino acid asparagine 273 (ASN 273) of target has shown hydrogen bond interaction with the top ranked ligand.
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Binbay, Nil E., and Berrin Ziyadanogullari. "Comparison of binding properties of a novel non-steroidal anti-inflammatory agent and ibuprofen to cyclooxygenase-1 and cyclooxygenase-2 enzymes by saturation transfer difference nuclear magnetic resonance." Canadian Journal of Physics 96, no. 7 (July 2018): 693–99. http://dx.doi.org/10.1139/cjp-2017-0759.
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Saturation transfer difference nuclear magnetic resonance is a ligand-based screening technique that focuses directly on the physical interaction of a macromolecule (protein, enzyme, etc.) and a small ligand. It is a powerful tool in pharmaceutical research. Here, a comparison is reported of the binding characteristics of ibuprofen and a novel anti-inflammatory agent to cyclooxygenase-1 and cyclooxygenase-2 enzymes as an application of saturation transfer difference nuclear magnetic resonance. It has been shown that this novel agent is capable of binding to both isoforms of the cyclooxygenase enzymes. It has also been reported that novel agent binds better to cyclooxygenase-2.
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Žúbor, Vladimír, Albert Breier, Marta Horváthová, Dagmar Hagarová, Peter Gemeiner, and Danica Mislovičová. "Purification of Glycerol Kinase by "Dye-Ligand" Chromatography and Hydrophobic Interaction Chromatography on Bead-Cellulose Derivatives." Collection of Czechoslovak Chemical Communications 58, no. 2 (1993): 445–51. http://dx.doi.org/10.1135/cccc19930445.
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The crude extract of cytosole enzymes was obtained from homogenized cells of Saccharomyces cerevisiae by partition. The enzyme was then isolated from the lower aqueous phase displaying higher glycerol kinase activity by dye-ligand chromatography on Cibacron Blue (CB) or Remazol Brilliant Blue R (RB)-derivatized bead-cellulose, ATP being the eluent. The specific activity of glycerol kinase rised more than 10 and 7-times after affinity dye-ligand chromatography and hydrophobic interaction chromatography, respectively. Glycerol kinase obtained by the latter method was purified by CB-bead cellulose. The final preparation maintained its enzymic activity without noticeable losses during a long-term storage at 4 °C in dark.
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Ulrichová, Jitka, Jan Kovář, and Vilím Šimánek. "Interaction of quaternary aromatic isoquinoline alkaloids with acetylcholinesterase from Electrophorus electricus." Collection of Czechoslovak Chemical Communications 50, no. 4 (1985): 978–83. http://dx.doi.org/10.1135/cccc19850978.
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Fluorescence data for the interaction of acetylcholinesterase (EC 3.1.1.7, ACHE) from Electrophorus electricus with berberine, 13-ethylberberine, coralyne, and chelerythrine have been presented. By a comparison with known inhibitors of acetylcholinesterase, tetramethylammonium and tacrine, the electrostatic interaction of quaternary alkaloids with the γ-anionic site of enzyme could be confirmed. During the interaction, two molecules of the ligand are bound to the molecule of the enzyme.
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Koentjoro, Maharani Pertiwi, Adyan Donastin, and Endry Nugroho Prasetyo. "POTENSI SENYAWA BIOAKTIF TANAMAN KELOR PENGHAMBAT INTERAKSI ANGIOTENSIN-CONVERTING ENZYME 2 PADA SINDROMA SARS-COV-2." Jurnal Bioteknologi & Biosains Indonesia (JBBI) 7, no. 2 (December 29, 2020): 259–70. http://dx.doi.org/10.29122/jbbi.v7i2.4156.
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The Potential of Moringa oleifera Bioactive Compounds for Inhibiting Angiotensin-Converting Enzyme 2 Interaction in SARS-Cov-2 Syndrome Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) disease (COVID-19) is a threat to human health. This infection is determined by the interaction of the spike S1 domain protein with angiotensin-converting enzyme 2 (ACE2) in the epithelial cells of the respiratory tract, especially the lungs. ACE2 inhibition is an important target in controlling COVID-19. Flavonoids of medicinal plants, are known to interfere with ACE (ACE2 homologous). Therefore, this study aims to explore the ability of apiin, epicatechin, and hesperetin from Moringa oleifera in interacting with the ACE2 using MOE 2008.10. The ligand molecules were prepared from PubChem database. The ACE2 protein was retrieved from Protein Data Bank (ID 1R4L) and analyzed for the active sites. Analysis of docking scores and hydrogen bonds of ACE2-ligand complex and active site showed that the affinity of flavonoids can be ranked as hesperetin > epicatechin > apiin > C19H23Cl2N3O4. The results provided computational information that apiin, epicatechin, and hesperetin have the potential to prevent COVID-19 infection. The prediction of activity spectra for substances (PASS) score showed the ligand displays antiviral activity. Infeksi severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pada pandemi coronavirus disease 2019 (COVID-19) menjadi ancaman dunia kesehatan saat ini. Infeksi SARS-CoV-2 ditentukan oleh interaksi protein spike envelope S1 domain dengan reseptor angiotensin-converting enzyme 2 (ACE2) yang diekspresikan pada sel epitel saluran pernafasan terutama paru-paru. Mekanisme penghambatan ACE2 menjadi target penting dalam pengendalian COVID-19. Senyawa bioaktif tanaman obat, seperti flavonoid diketahui mampu mengganggu fungsi banyak makromolekul termasuk ACE (homolog dengan ACE2). Penelitian ini bertujuan mengeksplorasi kemampuan senyawa apiin, epicatechin, dan hesperetin dari Moringa oleifera dalam berinteraksi dengan sisi aktif ACE2 menggunakan metode penambatan molekul. Studi dilakukan dengan preparasi struktur molekul ligan dari PubChem database dan diolah dengan MOE 2008.10. Selanjutnya, data protein ACE2 (Protein Data Bank ID 1R4L) dianalisis sisi aktifnya untuk mengetahui lokasi penambatan ligan senyawa. Analisis skor docking dan ikatan hydrogen komplek ligan dan sisi aktif ACE2 menunjukkan bahwa afinitas flavonoid dapat diperingkatkan sebagai afinitas hesperetin > epicatechin > apiin > C19H23Cl2N3O4. Ketiga ligan senyawa yang terkandung dalam M. oleifera secara in silico mampu mengikat sisi aktif ACE2, sehingga berpotensi mencegah infeksi COVID-19. Skor PASS (prediction of activity spectra for substances) menunjukkan aktivitas biologis ligan yang menyerupai antiviral.
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Harathi, N., Madhusudana Pulaganti, C. M. Anuradha, and Suresh Kumar Chitta. "Inhibition of Mycobacterium-RmlA by Molecular Modeling, Dynamics Simulation, and Docking." Advances in Bioinformatics 2016 (February 14, 2016): 1–13. http://dx.doi.org/10.1155/2016/9841250.
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The increasing resistance to anti-tb drugs has enforced strategies for finding new drug targets against Mycobacterium tuberculosis (Mtb). In recent years enzymes associated with the rhamnose pathway in Mtb have attracted attention as drug targets. The present work is on α-D-glucose-1-phosphate thymidylyltransferase (RmlA), the first enzyme involved in the biosynthesis of L-rhamnose, of Mtb cell wall. This study aims to derive a 3D structure of RmlA by using a comparative modeling approach. Structural refinement and energy minimization of the built model have been done with molecular dynamics. The reliability assessment of the built model was carried out with various protein checking tools such as Procheck, Whatif, ProsA, Errat, and Verify 3D. The obtained model investigates the relation between the structure and function. Molecular docking interactions of Mtb-RmlA with modified EMB (ethambutol) ligands and natural substrate have revealed specific key residues Arg13, Lys23, Asn109, and Thr223 which play an important role in ligand binding and selection. Compared to all EMB ligands, EMB-1 has shown better interaction with Mtb-RmlA model. The information thus discussed above will be useful for the rational design of safe and effective inhibitors specific to RmlA enzyme pertaining to the treatment of tuberculosis.
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Arathi, K. N., K. Abdul Khayum, Sulaiman Mohammed Alnasser, and Onsinyo James Meroka. "COVID-19 Protease Inhibitor using Azole N-Mannich Bases: A Molecular Docking Approach." Asian Journal of Chemistry 33, no. 5 (2021): 1031–38. http://dx.doi.org/10.14233/ajchem.2021.23100.
Full textAbstract:
Coronaviruses are the largest group of viruses belonging to the Nidovirales order, which includes Coronaviridae, Arteriviridae and Roniviridae families. In this work, a molecular modeling technique is adopted to find out the excellent moiety to inhibit the protease enzyme which is present in the coronavirus. Autodock 4.2 tool was used to find out the docking score of 32 ligands. The molinspiration server helps to find out the drug-likeness property and whether these ligands having a binding towards the protease enzyme. The synthetic N-Mannich bases of azole were docked with COVID-19 main protease in complex with an inhibitor N3 (PDB id: 6lu7). Among 32 ligand molecules, around 25 ligands showed an excellent binding score when compared to the standard drug favipiravir. The presence of dimethyl group in the pyrazole nucleus helps good interaction with protease enzyme. Among the Mannich bases, the secondary amine mannich base of piperazine considered as the best derivative to inhibit the protease enzyme.
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Medda, Pankaj, and Wilhelm Hasselbach. "Formation and Decay of the Vanadate Complex of the Sarcoplasmic Reticulum Calcium Transport Protein." Zeitschrift für Naturforschung C 40, no. 11-12 (October 1, 1985): 876–79. http://dx.doi.org/10.1515/znc-1985-11-1221.
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Abstract The calcium free sarcoplasmic reticulum calcium transport ATPase incorporates in the presence of magnesium ions approx. 8 nmol monovanadate per mg protein, indicating the formation of a complex containing one vanadate residue per enzyme molecule. On ligand-removal or dilution, the saturated enzyme complex displays biphasic decay kinetics, while the unsaturated complex slowly dissociates monophasically. - Ligand competition by raising the concentrations of unlabeled vanadate results in a progressive decrease of the dissociation rate of the unsaturated enzyme. The complicated dissociation kinetics indicate a sequential mode of interaction between two ligand binding sites. The one to one stoichiometry of the complex suggests that the two sites are located at adjacent ATPase molecules. - It appears unlikely that the decay of the enzyme, vanadate complex is retarded by the formation of a stable quaternary complex between the enzyme, magnesium, mono-and polyvanadate.
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HAYHURST, Graham P., Jacky HARLOW, Joey CHOWDRY, Esme GROSS, Emma HILTON, Martin S. LENNARD, Geoffrey T. TUCKER, and S. Wynne ELLIS. "Influence of phenylalanine-481 substitutions on the catalytic activity of cytochrome P450 2D6." Biochemical Journal 355, no. 2 (April 6, 2001): 373–79. http://dx.doi.org/10.1042/bj3550373.
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Homology models of the active site of cytochrome P450 2D6 (CYP2D6) have identified phenylalanine 481 (Phe481) as a putative ligand-binding residue, its aromatic side chain being potentially capable of participating in π-π interactions with the benzene ring of ligands. We have tested this hypothesis by replacing Phe481 with tyrosine (Phe481 → Tyr), a conservative substitution, and with leucine (Phe481 → Leu) or glycine (Phe481 → Gly), two non-aromatic residues, and have compared the properties of the wild-type and mutant enzymes in microsomes prepared from yeast cells expressing the appropriate cDNA-derived protein. The Phe481 → Tyr substitution did not alter the kinetics [Km (µM) and Vmax (pmol/min per pmol) respectively] of oxidation of S-metoprolol (27; 4.60), debrisoquine (46; 2.46) or dextromethorphan (2; 8.43) relative to the respective wild-type values [S-metoprolol (26; 3.48), debrisoquine (51; 3.20) and dextromethorphan (2; 8.16)]. The binding capacities [Ks (µM)] of a range of CYP2D6 ligands to the Phe481 → Tyr enzyme (S-metoprolol, 22.8; debrisoquine, 12.5; dextromethorphan, 2.3; quinidine, 0.13) were also similar to those for the wild-type enzyme (S-metoprolol, 10.9; debrisoquine, 8.9; dextromethorphan, 3.1; quinidine, 0.10). In contrast, the Phe481 → Leu and Phe481 → Gly substitutions increased significantly (3-16-fold) the Km values of oxidation of the three substrates [S-metoprolol (120-124µM), debrisoquine (152-184µM) and dextromethorphan (20-31µM)]. Similarly, the Ks values of the ligands to Phe481 → Leu and Phe481 → Gly mutants were also increased 3 to 10-fold (S-metoprolol, 33.2-41.9µM; debrisoquine, 85-90µM; dextromethorphan, 15.7-18.8µM; quinidine 0.35-0.53µM). However, contrary to a recent proposal that Phe481 has the dominant role in the binding of substrates that undergo CYP2D6-mediated N-dealkylation routes of metabolism, the Phe481 → Gly substitution did not substantially decrease the capacity of the enzyme to N-deisopropylate metoprolol (wild-type, 1.12pmol/min per pmol of P450; Phe481 → Gly, 0.71), whereas an Asp301 → Gly substitution decreased the N-dealkylation reaction by 95% of the wild-type rate. Overall, our results are consistent with the proposal that Phe481 is a ligand-binding residue in the active site of CYP2D6 and that the residue interacts with ligands via a π-π interaction between its phenyl ring and the aromatic moiety of the ligand. However, the relative importance of Phe481 in binding is ligand-dependent; furthermore, its importance is secondary to that of Asp301. Finally, contrary to predictions of a recent homology model, Phe481 does not seem to have a primary role in CYP2D6-mediated N-dealkylation.
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ELLIS, S. Wynne, Graham P. HAYHURST, Tracy LIGHTFOOT, Gillian SMITH, Jacky HARLOW, Karen ROWLAND-YEO, Cecilia LARSSON, et al. "Evidence that serine 304 is not a key ligand-binding residue in the active site of cytochrome P450 2D6." Biochemical Journal 345, no. 3 (January 25, 2000): 565–71. http://dx.doi.org/10.1042/bj3450565.
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Homology models of cytochrome P450 2D6 (CYP2D6) have identified serine 304 as an active-site residue and implicated a putative role for this residue in substrate enantioselectivity and the differential inhibition of enzyme activity by the diastereoisomers quinine and quinidine. The role of serine 304 in selectivity is thought to be achieved through a preferential hydrogen-bond interaction between the hydroxyl group of the residue and one of the stereoisomers of each ligand. We have tested this hypothesis by substituting serine 304 with alanine, a non-hydrogen-bonding residue, and compared the properties of the wild-type and mutant enzymes in microsomes prepared from yeast cells expressing the appropriate cDNA-derived enzyme. The Ser304Ala substitution did not alter the enantioselective oxidation of metoprolol; the O-demethylation reaction remained R-(+)-enantioselective (wild-type, RS, 1.7; mutant, RS, 1.6), whereas α-hydroxylation remained S-(-)-enantioselective (wild-type and mutant, R/S, 0.7). Similarly, the selective oxidation of the R-(+) and S-(-) enantiomers of propranolol to the major 4-hydroxy metabolite was identical with both wild-type and mutant forms of the enzyme (R/S 0.9), although the formation of minor metabolites (5-hydroxy and deisopropylpropranolol) did show some slight alteration in enantioselectivity. The differential inhibition of enzyme activity by quinine and quinidine was also identical with both forms of CYP2D6, the IC50 values for each enzyme being approx. 10 μM and 0.1 μM for quinine and quinidine, respectively. The kinetics of formation of α-hydroxymetoprolol and 4-hydroxydebrisoquine by wild-type and the Ser304Ala mutant was also very similar. However, modest changes in the regioselective oxidation of metoprolol and debrisoquine were observed with the Ser304Ala mutant. The regio- and enantioselective oxidation of an analogue of metoprolol, in which the hydroxyl group attached to the chiral carbon was replaced by a methyl moiety, was again identical with both wild-type and Ser304Ala mutant. However, the observed selectivity was the reverse of that observed with metoprolol. Collectively, these data indicate that Ser304 is unlikely to be a key ligand-binding residue, although the residue may indeed be located in the active-site cavity. The reversal of selectivity with the methyl analogue of metoprolol indicates that the hydroxyl group attached to the chiral centre of ligands, such as metoprolol, is important in defining the enzyme's selective properties, and that a hydrogen-bonding residue, other than Ser304, may be involved in this interaction. Current homology models of the active site of CYP2D6 that predict a hydrogen-bond interaction between Ser304 and specific ligands will need to be re-evaluated, and other candidate residues capable of such an interaction nominated and tested by site-directed mutagenesis studies.
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Madaj, Rafal, Bartlomiej Gostynski, Roza Pawlowska, and Arkadiusz Chworos. "Tissue-Nonspecific Alkaline Phosphatase (TNAP) as the Enzyme Involved in the Degradation of Nucleotide Analogues in the Ligand Docking and Molecular Dynamics Approaches." Biomolecules 11, no. 8 (July 27, 2021): 1104. http://dx.doi.org/10.3390/biom11081104.
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Tissue-nonspecific alkaline phosphatase (TNAP) is known to be involved in the degradation of extracellular ATP via the hydrolysis of pyrophosphate (PPi). We investigated, using three different computational methods, namely molecular docking, thermodynamic integration (TI) and conventional molecular dynamics (MD), whether TNAP may also be involved in the utilization of β,γ-modified ATP analogues. For that, we analyzed the interaction of bisphosphonates with this enzyme and evaluated the obtained structures using in silico studies. Complexes formed between pyrophosphate, hypophosphate, imidodiphosphate, methylenediphosphonic acid monothiopyrophosphate, alendronate, pamidronate and zoledronate with TNAP were generated and analyzed based on ligand docking, molecular dynamics and thermodynamic integration. The obtained results indicate that all selected ligands show high affinity toward this enzyme. The forming complexes are stabilized through hydrogen bonds, electrostatic interactions and van der Waals forces. Short- and middle-term molecular dynamics simulations yielded very similar affinity results and confirmed the stability of the protein and its complexes. The results suggest that certain effectors may have a significant impact on the enzyme, changing its properties.
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Wise, Courtney E., Anastasia E. Ledinina, and Carolyn E. Lubner. "Site-Differentiated Iron–Sulfur Cluster Ligation Affects Flavin-Based Electron Bifurcation Activity." Metabolites 12, no. 9 (September 1, 2022): 823. http://dx.doi.org/10.3390/metabo12090823.
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Electron bifurcation is an elegant mechanism of biological energy conversion that effectively couples three different physiologically relevant substrates. As such, enzymes that perform this function often play critical roles in modulating cellular redox metabolism. One such enzyme is NADH-dependent reduced-ferredoxin: NADP+ oxidoreductase (NfnSL), which couples the thermodynamically favorable reduction of NAD+ to drive the unfavorable reduction of ferredoxin from NADPH. The interaction of NfnSL with its substrates is constrained to strict stoichiometric conditions, which ensures minimal energy losses from non-productive intramolecular electron transfer reactions. However, the determinants for this are not well understood. One curious feature of NfnSL is that both initial acceptors of bifurcated electrons are unique iron–sulfur (FeS) clusters containing one non-cysteinyl ligand each. The biochemical impact and mechanistic roles of site-differentiated FeS ligands are enigmatic, despite their incidence in many redox active enzymes. Herein, we describe the biochemical study of wild-type NfnSL and a variant in which one of the site-differentiated ligands has been replaced with a cysteine. Results of dye-based steady-state kinetics experiments, substrate-binding measurements, biochemical activity assays, and assessments of electron distribution across the enzyme indicate that this site-differentiated ligand in NfnSL plays a role in maintaining fidelity of the coordinated reactions performed by the two electron transfer pathways. Given the commonality of these cofactors, our findings have broad implications beyond electron bifurcation and mechanistic biochemistry and may inform on means of modulating the redox balance of the cell for targeted metabolic engineering approaches.
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Syaban, Mokhamad, Nabila Erwan, Muhamad Syamsuddin, Fatimah Zahra, and Faradilah Sabila. "Molecular Docking Approach of Viscosin as Antibacterial for Methicillin-resistant Staphylococcus Aureus Via β-Lactamase Inhibitor Mechanism." Clinical and Research Journal in Internal Medicine 2, no. 2 (November 8, 2021): 187–92. http://dx.doi.org/10.21776/ub.crjim.2021.002.02.4.
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Background: β-lactamase is an enzyme that plays a role in the occurrence of antibiotic resistance against Methicillin-resistant Staphylococcus aureus (MRSA) bacteria. Viscosin is a lipopeptide biosurfactant produced by the Pseudomonas group bacteria. A study states that Viscosin has strong antibacterial properties. Aims: This study aims to determine the interactions that occur with Viscosin and β-lactamase enzymes. Methods: Researchers used the in-silico method to determine the molecular interactions that occurred computationally. The protein used was β-lactamase protein obtained from the Protein Data Bank and Viscosin ligand obtained from the PubChem web server, and we used native ligands as control. Pharma expert web server and Pyrx, Pymol, and Discovery Studio software were used in this research. Results: The results showed that Viscosin has high activity as an antibiotic and is predicted to be a membrane integrity antagonist. The binding affinity interaction that occurs between Viscosin-β-lactamase is -7.3 kcal/mol. The affinity is lower than the control. Conclusion: Viscosin was predicted to have strong antibacterial properties, but the binding interaction was lower than the control. However, exploration of Viscosin compounds and further research to determine the antibacterial effect of Viscosin against MRSA and other bacteria is needed to against antibiotic resistance.
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Kudlinzki, Denis, Verena L. Linhard, Krishna Saxena, Sridhar Sreeramulu, Santosh Gande, Ulrich Schieborr, Matthias Dreyer, and Harald Schwalbe. "High-resolution crystal structure of cAMP-dependent protein kinase fromCricetulus griseus." Acta Crystallographica Section F Structural Biology Communications 71, no. 8 (July 29, 2015): 1088–93. http://dx.doi.org/10.1107/s2053230x1501242x.
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Protein kinases (PKs) are dynamic regulators of numerous cellular processes. Their phosphorylation activity is determined by the conserved kinase core structure, which is maintained by the interaction and dynamics with associated domains or interacting proteins. The prototype enzyme for investigations to understand the activity and regulation of PKs is the catalytic subunit of cAMP-dependent protein kinase (PKAc). Major effects of functional regulation and ligand binding are driven by only minor structural modulations in protein–protein interactions. In order to resolve such minor structural differences, very high resolution structures are required. Here, the high-resolution X-ray structure of PKAc fromCricetulus griseusis reported.
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Kumar, Prashant, and Paulina Maria Dominiak. "Combining Molecular Dynamic Information and an Aspherical-Atom Data Bank in the Evaluation of the Electrostatic Interaction Energy in Multimeric Protein-Ligand Complex: A Case Study for HIV-1 Protease." Molecules 26, no. 13 (June 24, 2021): 3872. http://dx.doi.org/10.3390/molecules26133872.
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Computational analysis of protein–ligand interactions is of crucial importance for drug discovery. Assessment of ligand binding energy allows us to have a glimpse of the potential of a small organic molecule to be a ligand to the binding site of a protein target. Available scoring functions, such as in docking programs, all rely on equations that sum each type of protein–ligand interactions in order to predict the binding affinity. Most of the scoring functions consider electrostatic interactions involving the protein and the ligand. Electrostatic interactions constitute one of the most important part of total interactions between macromolecules. Unlike dispersion forces, they are highly directional and therefore dominate the nature of molecular packing in crystals and in biological complexes and contribute significantly to differences in inhibition strength among related enzyme inhibitors. In this study, complexes of HIV-1 protease with inhibitor molecules (JE-2147 and darunavir) were analyzed by using charge densities from the transferable aspherical-atom University at Buffalo Databank (UBDB). Moreover, we analyzed the electrostatic interaction energy for an ensemble of structures, using molecular dynamic simulations to highlight the main features of electrostatic interactions important for binding affinity.
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Na'imah, Janatun. "In silico study of COX-2 on indomethacin and diclofenac as nonsteroidal anti-inflammatory drugs (NSAIDs)." Farmasains : Jurnal Farmasi dan Ilmu Kesehatan 4, no. 1 (June 21, 2019): 31. http://dx.doi.org/10.22219/farmasains.v4i1.7767.
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Cyclooxygenase is an enzyme that plays a role in the formation of prostaglandins, which can cause inflammation and pain when overexpressed. This study aims to determine the interaction between COX-2 macromolecules (receptors) with their ligands, namely indomethacin and diclofenac in silico using the Molecular Docking method. The COX-2 receptor was downloaded in the form of a 3D structure from the RCSB GDP with code 5F19. Diclofenac Ligand and Indomethacin were downloaded in the form of a 3D structure from the RCSB GDP with 4ZBQ code and 4IK7 code. The results showed that the interaction between COX-2 and indomethacin was the interaction of hydrogen, which linked indomethacin with amino acid Leu531 and steric interactions between indomethacin and amino acids Trp387, Tyr385, Tyr355, Leu352, and Val523. The interaction of [COX-2 – Indomethacin] produces a value of ∆G of -103.136 kcal/mol, and the value of RMSD is 1.244 Å. Whereas, the interaction that occurs in COX-2 with diclofenac is the steric interaction that happens between diclofenac with amino acids Leu390, Trp387, Gln203, His388, His207, and Thr206. The interaction parameter between [COX-2-Diclofenac] obtained ∆G value of -7.843 kcal/mol and an RMSD value of 2.07851 Å.
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Sutherland, J., C. Greenwood, J. Peterson, and A. J. Thomson. "An investigation of the ligand-binding properties of Pseudomonas aeruginosa nitrite reductase." Biochemical Journal 233, no. 3 (February 1, 1986): 893–98. http://dx.doi.org/10.1042/bj2330893.
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The low-temperature e.p.r. and m.c.d. (magnetic-circular-dichroism) spectra of Pseudomonas aeruginosa nitrite reductase, together with those of its partially and fully cyanide-bound derivatives, were investigated. The m.c.d. spectra in the range 600-2000 nm indicate that the native axial ligands to haem c are histidine and methionine, and furthermore that it is the methionine ligand that must be displaced before cyanide binding at this haem. The m.c.d. spectra in the range 1000-2000 nm contain no charge-transfer bands arising from low-spin ferric haem d1, a chlorin. New optical transitions in the region 700-850 nm were found for the cyanide adduct of haem d1. The g-values of haem d1 in the native enzyme are 2.51, 2.43 and 1.71, suggesting co-ordination by two histidine ligands in the oxidized state. There is clear evidence in the e.p.r. data of an interaction between the c and d1 haem groups. This is not apparent in the optical spectra. The results are interpreted in terms of haem groups that are remote from each other, their interaction being mediated through protein conformational changes. The possible implications of this in relation to reduction processes catalysed by the enzyme are considered.
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Mori, Matteo, Stefania Villa, Samuele Ciceri, Diego Colombo, Patrizia Ferraboschi, and Fiorella Meneghetti. "An Outline of the Latest Crystallographic Studies on Inhibitor-Enzyme Complexes for the Design and Development of New Therapeutics against Tuberculosis." Molecules 26, no. 23 (November 23, 2021): 7082. http://dx.doi.org/10.3390/molecules26237082.
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The elucidation of the structure of enzymes and their complexes with ligands continues to provide invaluable insights for the development of drugs against many diseases, including bacterial infections. After nearly three decades since the World Health Organization’s (WHO) declaration of tuberculosis (TB) as a global health emergency, Mycobacterium tuberculosis (Mtb) continues to claim millions of lives, remaining among the leading causes of death worldwide. In the last years, several efforts have been devoted to shortening and improving treatment outcomes, and to overcoming the increasing resistance phenomenon. The structural elucidation of enzyme-ligand complexes is fundamental to identify hot-spots, define possible interaction sites, and elaborate strategies to develop optimized molecules with high affinity. This review offers a critical and comprehensive overview of the most recent structural information on traditional and emerging mycobacterial enzymatic targets. A selection of more than twenty enzymes is here discussed, with a special emphasis on the analysis of their binding sites, the definition of the structure–activity relationships (SARs) of their inhibitors, and the study of their main intermolecular interactions. This work corroborates the potential of structural studies, substantiating their relevance in future anti-mycobacterial drug discovery and development efforts.
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Velesinović, Aleksandar, and Goran Nikolić. "Protein-protein interaction networks and protein-ligand docking: Contemporary insights and future perspectives." Acta Facultatis Medicae Naissensis 38, no. 1 (2021): 5–17. http://dx.doi.org/10.5937/afmnai38-28322.
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Traditional research means, such as in vitro and in vivo models, have consistently been used by scientists to test hypotheses in biochemistry. Computational (in silico) methods have been increasingly devised and applied to testing and hypothesis development in biochemistry over the last decade. The aim of in silico methods is to analyze the quantitative aspects of scientific (big) data, whether these are stored in databases for large data or generated with the use of sophisticated modeling and simulation tools; to gain a fundamental understanding of numerous biochemical processes related, in particular, to large biological macromolecules by applying computational means to big biological data sets, and by computing biological system behavior. Computational methods used in biochemistry studies include proteomics-based bioinformatics, genome-wide mapping of protein-DNA interaction, as well as high-throughput mapping of the protein-protein interaction networks. Some of the vastly used molecular modeling and simulation techniques are Monte Carlo and Langevin (stochastic, Brownian) dynamics, statistical thermodynamics, molecular dynamics, continuum electrostatics, protein-ligand docking, protein-ligand affinity calculations, protein modeling techniques, and the protein folding process and enzyme action computer simulation. This paper presents a short review of two important methods used in the studies of biochemistry - protein-ligand docking and the prediction of protein-protein interaction networks.
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Jeffreys, Laura N., Kamila J. Pacholarz, Linus O. Johannissen, Hazel M. Girvan, Perdita E. Barran, Michael W. Voice, and Andrew W. Munro. "Characterization of the structure and interactions of P450 BM3 using hybrid mass spectrometry approaches." Journal of Biological Chemistry 295, no. 22 (April 17, 2020): 7595–607. http://dx.doi.org/10.1074/jbc.ra119.011630.
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The cytochrome P450 monooxygenase P450 BM3 (BM3) is a biotechnologically important and versatile enzyme capable of producing important compounds such as the medical drugs pravastatin and artemether, and the steroid hormone testosterone. BM3 is a natural fusion enzyme comprising two major domains: a cytochrome P450 (heme-binding) catalytic domain and a NADPH-cytochrome P450 reductase (CPR) domain containing FAD and FMN cofactors in distinct domains of the CPR. A crystal structure of full-length BM3 enzyme is not available in its monomeric or catalytically active dimeric state. In this study, we provide detailed insights into the protein-protein interactions that occur between domains in the BM3 enzyme and characterize molecular interactions within the BM3 dimer by using several hybrid mass spectrometry (MS) techniques, namely native ion mobility MS (IM-MS), collision-induced unfolding (CIU), and hydrogen-deuterium exchange MS (HDX-MS). These methods enable us to probe the structure, stoichiometry, and domain interactions in the ∼240 kDa BM3 dimeric complex. We obtained high-sequence coverage (88–99%) in the HDX-MS experiments for full-length BM3 and its component domains in both the ligand-free and ligand-bound states. We identified important protein interaction sites, in addition to sites corresponding to heme-CPR domain interactions at the dimeric interface. These findings bring us closer to understanding the structure and catalytic mechanism of P450 BM3.
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Umar, Abd Kakhar, Faruk Jayanto Kelutur, and James H. Zothantluanga. "Flavonoid Compounds of Buah Merah (Pandanus conoideus Lamk) as a Potent Oxidative Stress Modulator in ROS-induced Cancer: In Silico Approach." Majalah Obat Tradisional 26, no. 3 (December 21, 2021): 221. http://dx.doi.org/10.22146/mot.70177.
Full textAbstract:
Buah Merah, a typical fruit from Papua, Indonesia which is used empirically in cancer therapy is rich in carotenoids and flavonoids. However, the mechanisms by which Buah Merah ameliorates cancer remained unknown. Natural antioxidant enzymes and pro-oxidant enzymes modulation significantly suppressed ROS production and cancer growth. Therefore, the determination of target enzymes of Buah Merah contents was studied through an in silico approach. Carotenoid and flavonoid compounds from Buah Merah were docked to 7 ROS modulating enzymes using Autodock Vina and the interaction stability was studied using the CABS Flex 2.0 server. The crucial amino acids of each enzyme were determined using DockFlin and prediction of acute oral toxicity of each test ligand was studied using ProTox-II. Based on the molecular docking results, quercetin 3'-glucoside is the most potent compound in binding to CAT, GR, GPx, SOD, LOX, and NOX with binding energy values of -11.2, -9.7, -8.6, -10.2, -10.7, and -12.8 kcal/mol, respectively. Meanwhile, taxifolin 3-O-α-arabinopyranose produced the highest binding affinity of -10.0 kcal/mol at the XO. Each test ligand formed stable interactions with ROS modulating enzymes and formed bonds with crucial amino acids resulting in strong adhesion compared to native and reference ligands. The glucoside group of quercetin 3'-glucoside plays an essential role in determining the proper position in the attachment and supports the formation of hydrogen bonds with receptors. With low acute oral toxicity, it can be concluded that quercetin 3'-glucoside from Buah Merah is a potent oxidative stress modulator in cancer prevention and therapy.
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Afanasyev, V. V., A. G. Miroshnichenko, D. V. Buzanov, and Yu P. Orlov. "SPECIFICS OF ALCOHOL USE DISORDER IN PRE-HOSPITAL PRACTICES AND EMERGENCY UNIT." EMERGENCY MEDICAL CARE 21, no. 2 (September 14, 2020): 71–81. http://dx.doi.org/10.24884/2072-6716-2020-21-2-71-81.
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Ethanol intoxication is analyzed from the point of ethanol interaction with receptors and enzymes. Ethanol dependence is based on neurochemical misbalance, which is different in acute ethanol intoxication and withdrawal. It is shown that the clinical manifestation of ethanol intoxication and its complications depends on ligand-receptor and enzyme imbalances. Pharmacological approaches to the treatment of acute ethanol intoxication and its complications at the pre-hospital stage and in the emergency, unit are discussed.
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Jagannathan, Venkataseshan, Arthi Venkatesan, and Pragasam Viswanathan. "Kinetics and Computational Evaluation of Eugenol and Vanillic Acid on Inhibition of a Potential Enzyme of a Nosocomial Pathogen that Promotes Struvite Formation." Current Enzyme Inhibition 16, no. 2 (June 30, 2020): 162–71. http://dx.doi.org/10.2174/1573408016999200415115754.
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Background: Struvite/infection stone is one of the major clinical burdens in urinary tract infections that is caused by the ureolytic behavior of pathogenic bacteria. Objective: The current strategy for treating infective stones is mostly antibiotic therapy, which ends in promoting resistance to the organisms. Hence in the present study, we investigated two phytocompounds, eugenol (an allyl-substituted guaiacol) and vanillic acid (a phenolic acid) that are found to be effective in inhibiting the urease enzyme of a nosocomial pathogen Proteus mirabilis. Methods: The enzyme was purified to apparent homogeneity and the kinetic parameters were studied in the presence and in the absence of eugenol and vanillic acid. Molecular docking and simulation were done to understand the level of protein-ligand interactions and the interacting residues. Results: Kinetic parameters obtained from the Michaelis-Menten plot show that both eugenol and vanillic acid exhibit non-competitive inhibition of urease enzyme in a dose-dependent manner. In silico studies showed that eugenol and vanillic acid have almost similar binding affinities to the regulatory pocket of the modeled protein. Dynamics and simulation results indicate that the interaction of ligands with the ARG373 residue of the protein provides a stable bound conformation. Conclusion: Overall, our results suggest that both the phytocompounds eugenol and vanillic acid have a potential application as a new therapy for the inhibition of urease enzyme that could possibly replace the complexions related to struvite stone formation.
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Forte, Elena, Alessandro Giuffrè, Li-shar Huang, Edward A. Berry, and Vitaliy B. Borisov. "Nitric Oxide Does Not Inhibit but Is Metabolized by the Cytochrome bcc-aa3 Supercomplex." International Journal of Molecular Sciences 21, no. 22 (November 12, 2020): 8521. http://dx.doi.org/10.3390/ijms21228521.
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Nitric oxide (NO) is a well-known active site ligand and inhibitor of respiratory terminal oxidases. Here, we investigated the interaction of NO with a purified chimeric bcc-aa3 supercomplex composed of Mycobacterium tuberculosis cytochrome bcc and Mycobacterium smegmatisaa3-type terminal oxidase. Strikingly, we found that the enzyme in turnover with O2 and reductants is resistant to inhibition by the ligand, being able to metabolize NO at 25 °C with an apparent turnover number as high as ≈303 mol NO (mol enzyme)−1 min−1 at 30 µM NO. The rate of NO consumption proved to be proportional to that of O2 consumption, with 2.65 ± 0.19 molecules of NO being consumed per O2 molecule by the mycobacterial bcc-aa3. The enzyme was found to metabolize the ligand even under anaerobic reducing conditions with a turnover number of 2.8 ± 0.5 mol NO (mol enzyme)−1 min−1 at 25 °C and 8.4 µM NO. These results suggest a protective role of mycobacterial bcc-aa3 supercomplexes against NO stress.
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Afriani Arif, Nurul, Rezki, and Irwandi Rahmat. "MOLACULAR DOCKING SENYAWA XANTHORRHIZOL DARI CURCUMA XANTHORRIZA SEBAGAI ANTI INFLAMASI DAN TES ADME PREDICTIONS." Jurnal Suara Kesehatan 8, no. 2 (August 29, 2022): 37–43. http://dx.doi.org/10.56836/journaliskb.v8i2.64.
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Abstract. Enzymes that influence the inflammatory process are cyclooxygenase enzymes that function in forming a prostaglandin to form inflammation. The xanthorrhizol compound has anti-inflammatory effect, so the xanthorrhizol docking research was carried out on the cycloocxigenase enzyme to determine the interaction of xanthorrhizol compounds derived from ginger rhizome (Curcuma xanthorriza). The analysis of these compounds used bioinformatics with several software namely PyMOL v.7.4.5, PyRx 0.8, and Avogadro. This software helps to visualize the compound and see the potential inhibitor of the compound against the cyclooxygenase enzyme. The docking of the xanthorrhizol ligand obtained the -7.4 binding affinity which showed it could interact with the active site of the cyclooxygenase enzyme target protein..
Abstrak. Enzim yang berpengaruh dalam proses inflamasi yaitu enzim cyclooxygenase yang berfungsi dalam membentuk sebua prostaglandin untuk membenntuk inflamasi. Senyawa xanthorrhizol mempunyai efek antiinflamasi, sehingga dilakukan penelitian docking xanthorrhizol terhadap enzim cycloocxigenase untuk mengetahui interaksi senyawa xanthorrhizol yang berasal dari tanaman temulawak (Curcuma xanthorriza) analisis senyawa tersebut menggunakan bioinformatika dengan beberapa soft ware yaitu PyMOL v.7.4.5, PyRx 0.8, dan Avogadro. Softwere ini membantu untuk memvisualisasi senyawa dan melihat potensi inhibitor senyawa terhadap enzim cyclooxigenase. Hasil docking dari ligan xanthorrhizol memproleh binding affinity -7,4 yang menunjukkan dapat berinteraksi dengan sisi aktif protein target enzim ciclooxigenase
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Menezes, Thaís Meira, Sinara Mônica Vitalino de Almeida, Ricardo Olímpio de Moura, Gustavo Seabra, Maria do Carmo Alves de Lima, and Jorge Luiz Neves. "Spiro-acridine inhibiting tyrosinase enzyme: Kinetic, protein-ligand interaction and molecular docking studies." International Journal of Biological Macromolecules 122 (February 2019): 289–97. http://dx.doi.org/10.1016/j.ijbiomac.2018.10.175.
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Kusamoto, Hiroshi, Akio Shiba, Masaya Tsunehiro, Haruto Fujioka, Emiko Kinoshita-Kikuta, Eiji Kinoshita, and Tohru Koike. "A simple method for determining the ligand affinity toward a zinc-enzyme model by using a TAMRA/TAMRA interaction." Dalton Transactions 47, no. 6 (2018): 1841–48. http://dx.doi.org/10.1039/c7dt04364c.
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Chakraborty, Sandeep. "DOCLASP - Docking ligands to target proteins using spatial and electrostatic congruence extracted from a known holoenzyme and applying simple geometrical transformations." F1000Research 3 (June 16, 2016): 262. http://dx.doi.org/10.12688/f1000research.5145.3.
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The ability to accurately and effectively predict the interaction between proteins and small drug-like compounds has long intrigued researchers for pedagogic, humanitarian and economic reasons. Protein docking methods (AutoDock, GOLD, DOCK, FlexX and Glide to name a few) rank a large number of possible conformations of protein-ligand complexes using fast algorithms. Previously, it has been shown that structural congruence leading to the same enzymatic function necessitates the congruence of electrostatic properties (CLASP). The current work presents a methodology for docking a ligand into a target protein, provided that there is at least one known holoenzyme with ligand bound - DOCLASP (Docking using CLASP). The contact points of the ligand in the holoenzyme defines a motif, which is used to query the target enzyme using CLASP. If there are significant matches, the holoenzyme and the target protein are superimposed based on congruent atoms. The same linear and rotational transformations are also applied to the ligand, thus creating a unified coordinate framework having the holoenzyme, the ligand and the target enzyme. In the current work, the dipeptidyl peptidase-IV inhibitor vildagliptin was docked to the PI-PLC structure complexed with myo-inositol using DOCLASP. Also, corroboration of the docking of phenylthiourea to the modelled structure of polyphenol oxidase (JrPPO1) from walnut is provided based on the subsequently solved structure of JrPPO1 (PDBid:5CE9). Analysis of the binding of the antitrypanosomial drug suramin to nine non-homologous proteins in the PDB database shows a diverse set of binding motifs, and multiple binding sites in the phospholipase A2-likeproteins from the Bothrops genus of pitvipers. The conformational changes in the suramin molecule on binding highlights the challenges in docking flexible ligands into an already ’plastic’ binding site. Thus, DOCLASP presents a method for ’soft docking’ ligands to proteins with low computational requirements.
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Yasmeen, Shagufta, and Promila Gupta. "Interaction of Selected Terpenoids From Dalbergia sissoo With Catalytic Domain of Matrix Metalloproteinase-1: An In Silico Assessment of Their Anti-wrinkling Potential." Bioinformatics and Biology Insights 13 (January 2019): 117793221989653. http://dx.doi.org/10.1177/1177932219896538.
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Matrix metalloproteinase-1 (MMP-1) is a predominant collagenase enzyme that cleaves collagen fibers, contributing to skin wrinkling. Matrix metalloproteinase-1 inhibitors of herbal origin may provide an earnest probability to offer a novel curative approach against MMP-1-mediated collagenolysis, prompted by ultraviolet (UV)-induced overexpression of MMP-1. In this in silico study, we have explored the MMP-1 inhibitory potential of selected terpenoids from Dalbergia sissoo extracts. Two triterpenoids (lupeol and betulin), 1 diterpenoid (phytol), and 1 ester derivative of lupeol (lupeol acetate) were studied along with a reference inhibitor (doxycycline) using molecular docking approach. Non covalent interaction between the target ligands was found. Lupeol was found interacting with amino acid (AA) residues in the catalytic domain of MMP-1 with 3 hydrogen bonds (H-bond) formation, phytol with 1 and doxycycline with 2 H-bonds, whereas betulin and lupeol acetate were not able to form any H-bond with the AA residues in the catalytic site of the target protein. However, hydrophobic interaction between these ligands and protein was evident with select residues. The binding affinity of lupeol was highest (binding free energy, Δ G = −8.24 kcal/mol), which was greater than reference drug, doxycycline (Δ G = −8.05 kcal/mol). Lupeol acetate and phytol displayed a Δ G value of −7.12 and −7.06 kcal/mol, respectively, whereas betulin holds less binding affinity for the target receptor (Δ G = −4.66 kcal/mol). In silico pharmacokinetic studies demonstrated drug-like properties of the ligand compounds. This study shows that hydroxyl groups present in the ligands play a substantial role in establishing protein ligand interaction via hydrogen bonding.
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Barak, Dov, Arie Ordentlich, Dana Stein, Qian-sheng Yu, Nigel H. Greig, and Avigdor Shafferman. "Accommodation of physostigmine and its analogues by acetylcholinesterase is dominated by hydrophobic interactions." Biochemical Journal 417, no. 1 (December 12, 2008): 213–22. http://dx.doi.org/10.1042/bj20081276.
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The role of the functional architecture of the HuAChE (human acetylcholinesterase) in reactivity toward the carbamates pyridostigmine, rivastigmine and several analogues of physostigmine, that are currently used or considered for use as drugs for Alzheimer's disease, was analysed using over 20 mutants of residues that constitute the interaction subsites in the active centre. Both steps of the HuAChE carbamylation reaction, formation of the Michaelis complex as well as the nucleophilic process, are sensitive to accommodation of the ligand by the enzyme. For certain carbamate/HuAChE combinations, the mode of inhibition shifted from a covalent to a noncovalent type, according to the balance between dissociation and covalent reaction rates. Whereas the charged moieties of pyridostigmine and rivastigmine contribute significantly to the stability of the corresponding HuAChE complexes, no such effect was observed for physostigmine and its analogues, phenserine and cymserine. Moreover, physostigmine-like ligands carrying oxygen instead of nitrogen at position −1 of the tricyclic moiety (physovenine and tetrahydrofurobenzofuran analogues) displayed comparable structure–function characteristics toward the various HuAChE enzymes. The essential role of the HuAChE hydrophobic pocket, comprising mostly residues Trp86 and Tyr337, in accommodating (−)-physostigmine and in conferring ∼300-fold stereoselectivity toward physostigmines, was elucidated through examination of the reactivity of selected HuAChE mutations toward enantiomeric pairs of different physostigmine analogues. The present study demonstrates that certain charged and uncharged ligands, like analogues of physostigmine and physovenine, seem to be accommodated by the enzyme mostly through hydrophobic interactions.
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Douglas, Ross G., Rajni K. Sharma, Geoffrey Masuyer, Lizelle Lubbe, Ismael Zamora, K. Ravi Acharya, Kelly Chibale, and Edward D. Sturrock. "Fragment-based design for the development of N-domain-selective angiotensin-1-converting enzyme inhibitors." Clinical Science 126, no. 4 (October 22, 2013): 305–13. http://dx.doi.org/10.1042/cs20130403.
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Zubair, Muhammad Sulaiman, Saipul Maulana, and Alwiyah Mukaddas. "Penambatan Molekuler dan Simulasi Dinamika Molekuler Senyawa Dari Genus Nigella Terhadap Penghambatan Aktivitas Enzim Protease HIV-1." Jurnal Farmasi Galenika (Galenika Journal of Pharmacy) (e-Journal) 6, no. 1 (March 7, 2020): 132–40. http://dx.doi.org/10.22487/j24428744.2020.v6.i1.14982.
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Nigella plant genus has potential as anti-HIV. One species of Nigella, Nigella sativa has been reported to have HIV-1 protease enzyme inhibitory activity. This research aims to determine the compounds of the Nigella genus that have activity as HIV-1 protease enzyme inhibitory activity through molecular docking method by Autodock Vina and to compare interaction stability through molecular dynamics simulations by AMBER. The metabolite of the Nigella genus was obtained from the KnapSack website, and enzyme model was obtained from the Protein Data Bank (3NU3). The results of molecular docking found the lowest affinity energy of Nigella compound is Nigellidine 4-O-sulfite (-13.4 kcal/mol). Meanwhile, the affinity energy of the ligand native (Amprenavir) was -12.1 kcal/mol. The lowest affinity energy of Nigellidine 4-O-sulfite might be predicted to have potency as an HIV-1 Protease inhibitor. Molecular dynamics simulation showed Root Mean Square Fluctuation (RMSF) value of Nigellidine 4-O-sulfite with the amino acid active site is 0.4064 Å for ASP:25 and 0.5667 Å for ASP: 125. Whereas RMSF ligand native with the amino acid active site, ASP: 25 is 0.3647 Å and ASP: 125 is 0.3639 Å. The higher RMSF value of Nigellidine 4-O-sulfite describes the lower interaction stability than the ligand native.
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Fitrilia, Tiana, M. Fakih Kurniawan, Febryana Rahayu Kurniawati, and Tirta Setiawan. "The POTENTIAL OF BUTTERFLY PEA FLOWER METHANOL EXTRACT AS AN ANTIOXIDANT BY IN SILICO." Indonesian Journal of Applied Research (IJAR) 1, no. 3 (December 28, 2020): 163–69. http://dx.doi.org/10.30997/ijar.v1i3.64.
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Abstract: Butterfly pea flower (Clitoria ternatea L.) is a flowering plant from the Fabecea family that can grow vines. Butterfly pea flower are known to have chemical components that can act as antioxidants. This study aims to predict the potential of active compounds from methanol extract of butterfly pea flower in inhibiting reactive oxygen species (ROS) based on bond affinity (∆G), the value of Root Mean Square Deviation (RMSD) and their interactions. The method used was a computational method with in silico technique. The software used was Autodock Vina with visualization using the Biovia Discovery Studio Visualizer 2020. The enzyme receptor was NADPH Oxidase (NOX) obtained from Protein Data Bank and the test ligands were a chemical compound from methanol extract of butterfly pea flower. The results of the in silico study showed that the NO had a innate ligand, namely the GTP ligand which has a ∆G value of -7.3 kcal/mol, an RMSD value of 3.1111 Å and the interaction with the receptor that involves the presence of hydrogen bonds. Based on the results of the analysis of 11 test ligands, the chemical component of caffeine was predicted to have the most potential in inhibiting ROS compounds with a value of ∆G -5.4, RMSD value of 1.328 Å and had the same amino acid residue in hydrogen bonding, namely ASP118, and GLY15. The test ligand had the ability to inhibit ROS compounds with a lower level of stability than the innate ligand.
Keywords: antioxidant; butterfly pea flower; in silico; NADPH oxidase, ROS
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Nagy, Péter, and Gábor Náray-Szabó. "Electrostatic lock-and-key model for the analysis of inhibitor recognition by dihydrofolate reductase." Canadian Journal of Chemistry 63, no. 7 (July 1, 1985): 1694–98. http://dx.doi.org/10.1139/v85-284.
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We propose a simple electrostatic model for the analysis of ligand binding to proteins. Besides a geometric fit electrostatic complementarity is also needed to allow favourable hydrogen bonding and ion-pair interactions. Nonpolar regions of the ligand and the biomacromolecule active site should match to reduce unfavourable hydrophobic effects, i.e., to lower the Gibbs free energy of the complex in aqueous solution. These principles are applied to the inhibition of dihydrofolate reductase by methotrexate. The enzyme active site is represented by an electrostatic lock which is derived from the macromolecular electrostatic potential and field at certain reference points. The key, defined similarly for the ligand, should fit into the lock to ensure complementarity, i.e., recognition. Hydrogen bonding and ion-pair interactions can be studied by the "potential key" while the "field key" accounts for hydrophobic complementarity. Analyzing the dihydrofolate reductase–methotrexate interaction in the light of the above principles the relative importance of various molecular fragments in binding can be determined.