Journal articles: 'Standard Binding Free Energy'

1

Kötter, Alex, Henning D. Mootz, and Andreas Heuer. "Standard Binding Free Energy of a SIM–SUMO Complex." Journal of Chemical Theory and Computation 15, no. 11 (September 17, 2019): 6403–10. http://dx.doi.org/10.1021/acs.jctc.9b00428.

Full text

APA, Harvard, Vancouver, ISO, and other styles

2

General, Ignacio J. "A Note on the Standard State’s Binding Free Energy." Journal of Chemical Theory and Computation 6, no. 8 (July 15, 2010): 2520–24. http://dx.doi.org/10.1021/ct100255z.

Full text

APA, Harvard, Vancouver, ISO, and other styles

3

Zhang, Hong, Hugo Gattuso, Elise Dumont, Wensheng Cai, Antonio Monari, Christophe Chipot, and François Dehez. "Accurate Estimation of the Standard Binding Free Energy of Netropsin with DNA." Molecules 23, no. 2 (January 25, 2018): 228. http://dx.doi.org/10.3390/molecules23020228.

Full text

APA, Harvard, Vancouver, ISO, and other styles

4

Doudou, Slimane, Neil A. Burton, and Richard H. Henchman. "Standard Free Energy of Binding from a One-Dimensional Potential of Mean Force." Journal of Chemical Theory and Computation 5, no. 4 (March 10, 2009): 909–18. http://dx.doi.org/10.1021/ct8002354.

Full text

APA, Harvard, Vancouver, ISO, and other styles

5

Jandova, Zuzana, Willem Jespers, Eddy Sotelo, Hugo Gutiérrez-de-Terán, and Chris Oostenbrink. "Free-Energy Calculations for Bioisosteric Modifications of A3 Adenosine Receptor Antagonists." International Journal of Molecular Sciences 20, no. 14 (July 16, 2019): 3499. http://dx.doi.org/10.3390/ijms20143499.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

Adenosine receptors are a family of G protein-coupled receptors with increased attention as drug targets on different indications. We investigate the thermodynamics of ligand binding to the A3 adenosine receptor subtype, focusing on a recently reported series of diarylacetamidopyridine inhibitors via molecular dynamics simulations. With a combined approach of thermodynamic integration and one-step perturbation, we characterize the impact of the charge distribution in a central heteroaromatic ring on the binding affinity prediction. Standard charge distributions according to the GROMOS force field yield values in good agreement with the experimental data and previous free energy calculations. Subsequently, we examine the thermodynamics of inhibitor binding in terms of the energetic and entropic contributions. The highest entropy penalties are found for inhibitors with methoxy substituents in meta position of the aryl groups. This bulky group restricts rotation of aromatic rings attached to the pyrimidine core which leads to two distinct poses of the ligand. Our predictions support the previously proposed binding pose for the o-methoxy ligand, yielding in this case a very good correlation with the experimentally measured affinities with deviations below 4 kJ/mol.

6

Lanez, Touhami, and Meriem Henni. "Spectrophotometrical study of antioxidant standards interacting with 2,2-diphenyl-1-picrylhydrazyl radical." Chemistry & Chemical Technology 10, no. 3 (September 15, 2016): 255–58. http://dx.doi.org/10.23939/chcht10.03.255.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

This work aims to study the interaction of four well known antioxidant standards with 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) using spectrophotometric assays. The binding parameters like binding constant and binding free energy of the free and DPPH• bound forms were determined. The determination is based upon the decrease in absorbance of the electronic absorption spectrum of an acetonitrile solution of DPPH• in the presence of gradually increasing amount of antioxidant standards.

7

Kaur, Jasmeet, Harsh Kumar, and Pamita Awasthi. "An Investigation on Drug Binding Ability of Cationic Surfactant CTAB." ECS Transactions 107, no. 1 (April 24, 2022): 5293–303. http://dx.doi.org/10.1149/10701.5293ecst.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

Taking in consideration the application of surfactants in drug delivery, the interactions of cationic surfactant cetyltrimethylammonium bromide (CTAB) with drug Betaine Hydrochloride have been scrutinized. The micellization behaviour of surfactant is investigated at three different temperatures (298.15, 308.15, and 318.15)K in presence of various concentrations (0.10, 0.25, and 0.50) mmolkg-1 of drug Betaine hydrochloride via conductivity measurements The critical micelle concentration (CMC) attained though conductometric measurements has been utilized to obtain different thermodynamic parameters of micellization i.e. standard free energy of micellization (ΔG0 m), standard enthalpy of micellization (ΔH0 m), and standard entropy of micellization (ΔS0 m).

8

La, Van N. T., and David D. L. Minh. "Bayesian Regression Quantifies Uncertainty of Binding Parameters from Isothermal Titration Calorimetry More Accurately Than Error Propagation." International Journal of Molecular Sciences 24, no. 20 (October 11, 2023): 15074. http://dx.doi.org/10.3390/ijms242015074.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

We compare several different methods to quantify the uncertainty of binding parameters estimated from isothermal titration calorimetry data: the asymptotic standard error from maximum likelihood estimation, error propagation based on a first-order Taylor series expansion, and the Bayesian credible interval. When the methods are applied to simulated experiments and to measurements of Mg(II) binding to EDTA, the asymptotic standard error underestimates the uncertainty in the free energy and enthalpy of binding. Error propagation overestimates the uncertainty for both quantities, except in the simulations, where it underestimates the uncertainty of enthalpy for confidence intervals less than 70%. In both datasets, Bayesian credible intervals are much closer to observed confidence intervals.

9

udhe, Prashik B. D., and Hardik G. Bhatt. "Molecular docking studies of some novel 2 & 3-(4-aminobenzamido) benzoic acid derivatives as DHFR inhibitors for treatment of tuberculosis." International Journal of PharmTech Research 13, no. 3 (2020): 262–71. http://dx.doi.org/10.20902/ijptr.2019.130317.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

A Novel series 2 & 3-(4-aminobenzamido) benzoic acid derivatives were designed virtually considering the basic pharmacophore N-(3,5-bis (trifluoromethyl) phenyl)- 5-chloro-2-hydroxybenzamide.The energy minimized conformers of each molecule was generated and docked with M. tuberculosis DHFR enzyme with PDB id: 1DF7 using Autodock 4.2.5.1. Most of the molecules have shown significant binding interaction with the receptor. Among the test compounds, DX-35, DY-24, DX-18, DX-31 & DY-23 have shown highest free energy of binding -9.51 to -8.92 kcal/mol and also the very good estimated inhibitory constant in a range of 0.11 to 0.29 Ki μM, which is comparable to that of the reference standard methotrexate and the standard Anti-Tb drug Ciprofloxacin.

10

Bertazzo, Martina, Dorothea Gobbo, Sergio Decherchi, and Andrea Cavalli. "Machine Learning and Enhanced Sampling Simulations for Computing the Potential of Mean Force and Standard Binding Free Energy." Journal of Chemical Theory and Computation 17, no. 8 (July 14, 2021): 5287–300. http://dx.doi.org/10.1021/acs.jctc.1c00177.

Full text

APA, Harvard, Vancouver, ISO, and other styles

11

Hamelberg, Donald, and J. Andrew McCammon. "Standard Free Energy of Releasing a Localized Water Molecule from the Binding Pockets of Proteins: Double-Decoupling Method." Journal of the American Chemical Society 126, no. 24 (June 2004): 7683–89. http://dx.doi.org/10.1021/ja0377908.

Full text

APA, Harvard, Vancouver, ISO, and other styles

12

HE, GANG, JUYING SHI, YANTAO CHEN, YI CHEN, QIANLING ZHANG, MINGLIANG WANG, and JIANHONG LIU. "RANK-ORDERING THE BINDING AFFINITY FOR FKBP12 AND H1N1 NEURAMINIDASE INHIBITORS IN THE COMBINATION OF A PROTEIN MODEL WITH DENSITY FUNCTIONAL THEORY." Journal of Theoretical and Computational Chemistry 10, no. 04 (August 2011): 541–65. http://dx.doi.org/10.1142/s0219633611006633.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

The quantum mechanical interaction energies between FKBP12 as well as H1N1 neuraminidase and their inhibitors were directly calculated with an efficient density functional theory by mimicking the whole protein with a protein model composed of the amino acids surrounding the ligands. It was found that the calculated quantum mechanical interaction energies correlate well with the experimental binding free energies with the correlation coefficients of 0.88, 0.86, and the standard deviation of 0.93 and 1.00 kcal/mol, respectively. To compare with force field approach, the binding free energies with the correlation coefficient R = 0.80 and 0.47 were estimated by AutoDock 4.0 programs. It was indicated that the quantum interaction energy shows a better performance in rank-ordering the binding affinity between FKBP12 and H1N1 neuraminidase inhibitors than those of AutoDock 4.0 program. In combination protein model with density functional theory, the estimated quantum interaction energy could be a good predictor or scoring function in structure-based computer-aided drug design. Finally, five new FKBP12 inhibitors were designed based on calculated quantum mechanical interaction energy. In particular, the theoretical K i value of one compound is as low as 0.05 nM, nearly 8-fold more active than FK506.

13

AL-Lame, Asmaa J. i., Wafaa F. Rodhan, Nafeesa J. Kadhim, and Shahed K. Taher. "Synthesis, Spectral Study and Theoretical Treatment of 2-(2-(4-bromocyclohexa-1, 3-dienyl)-4-oxo-2H- benz [1, 3] oxazin-3(4H)-ylamino)-2-oxoethyl carbamimidothioate and Derivatives." Journal of Advanced Sciences and Engineering Technologies 5, no. 1 (January 6, 2022): 1–7. http://dx.doi.org/10.32441/jaset.05.01.01.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

The standard heat of formation (ΔHof) and binding energy (ΔEb) for the free compound and their derivatives are calculated by using the PM3 method at 273K of Hyperchem.-8.07 program. The compound is more stable than their derivatives. furthermore to investigate the reactive site of the molecules the electrostatic potential of free derivatives is measured and pm3 is used to evaluate the vibrational spectra of the free derivatives, the frequencies are obtained approximately agreed with those values experimentally found; in addition, the calculation helps to assign clearly the most diagnostic bands .

14

Arowosegbe, Michael A., Oluwamuyiwa T. Amusan, Segun A. Adeola, Oluwatosin B. Adu, Israel A. Akinola, Bimpe F. Ogungbe, Olaposi I. Omotuyi, et al. "Kaempferol as a Potential PAK4 Inhibitor in Triple Negative Breast Cancer: Extra Precision Glide Docking and Free Energy Calculation." Current Drug Discovery Technologies 17, no. 5 (December 23, 2020): 682–95. http://dx.doi.org/10.2174/1570163816666190823135948.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

Background: P-21 activating kinase 4 (PAK4) is implicated in poor prognosis of many human tumors, particularly in Triple Negative Breast Cancer (TNBC) progression. Studies have revealed the crucial role of PAK4 in cell proliferation, anchorage-independent growth and cell migration among other hallmarks of cancer. Thus, PAK4 is an attractive target for anti-TNBC drug design and development. In our research, we used in silico methods to investigate the inhibitory potentials of kaempferol against PAK4 as compared with co-crystallized 4T6 and a standard PAK4 inhibitor-KPT-9274. The ligands were docked into the ATP-binding site of the target enzyme and post-docking validations were calculated. Results: In the molecular docking results, kaempferol had higher affinity than the standard KPT-9274. However, the SP and XP docking scores for the co-crystallized 4T6 were the highest. The analyses of the docking showed a favorable interaction between kaempferol and the catalytic-important aminoacyl residues, especially GLU396, LEU398 and ASP458 in the ATP-binding site of PAK4 when compared with what was obtained in the 4T6-PAK4 complex. Molecular mechanics based MM-GBSA was used to validate docking results. The free energy calculations revealed that kaempferol may have a favorable biological activity. Furthermore, the druggability of each ligand was assessed using the QikProp module and the SwissADME online tool. Kaempferol possessed a propitious drug-like property when compared to the standard ligands. Conclusions: We, therefore, put forward a logical argument that kaempferol can be further evaluated as a potential PAK4 inhibitor in TNBC.

15

Liu, Xiao, Lei Zheng, Chu Qin, Yalong Cong, John Z. H. Zhang, and Zhaoxi Sun. "Comprehensive Evaluation of End-Point Free Energy Techniques in Carboxylated-Pillar[6]arene Host–Guest Binding: III. Force-Field Comparison, Three-Trajectory Realization and Further Dielectric Augmentation." Molecules 28, no. 6 (March 19, 2023): 2767. http://dx.doi.org/10.3390/molecules28062767.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

Host–guest binding, despite the relatively simple structural and chemical features of individual components, still poses a challenge in computational modelling. The extreme underperformance of standard end-point methods in host–guest binding makes them practically useless. In the current work, we explore a potentially promising modification of the three-trajectory realization. The alteration couples the binding-induced structural reorganization into free energy estimation and suffers from dramatic fluctuations in internal energies in protein–ligand situations. Fortunately, the relatively small size of host–guest systems minimizes the magnitude of internal fluctuations and makes the three-trajectory realization practically suitable. Due to the incorporation of intra-molecular interactions in free energy estimation, a strong dependence on the force field parameters could be incurred. Thus, a term-specific investigation of transferable GAFF derivatives is presented, and noticeable differences in many aspects are identified between commonly applied GAFF and GAFF2. These force-field differences lead to different dynamic behaviors of the macrocyclic host, which ultimately would influence the end-point sampling and binding thermodynamics. Therefore, the three-trajectory end-point free energy calculations are performed with both GAFF versions. Additionally, due to the noticeable differences between host dynamics under GAFF and GAFF2, we add additional benchmarks of the single-trajectory end-point calculations. When only the ranks of binding affinities are pursued, the three-trajectory realization performs very well, comparable to and even better than the regressed PBSA_E scoring function and the dielectric constant-variable regime. With the GAFF parameter set, the TIP3P water in explicit solvent sampling and either PB or GB implicit solvent model in free energy estimation, the predictive power of the three-trajectory realization in ranking calculations surpasses all existing end-point methods on this dataset. We further combine the three-trajectory realization with another promising modified end-point regime of varying the interior dielectric constant. The combined regime does not incur sizable improvements for ranks and deviations from experiment exhibit non-monotonic variations.

16

Hu, Xiao, Irene Maffucci, and Alessandro Contini. "Advances in the Treatment of Explicit Water Molecules in Docking and Binding Free Energy Calculations." Current Medicinal Chemistry 26, no. 42 (January 8, 2020): 7598–622. http://dx.doi.org/10.2174/0929867325666180514110824.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

Background: The inclusion of direct effects mediated by water during the ligandreceptor recognition is a hot-topic of modern computational chemistry applied to drug discovery and development. Docking or virtual screening with explicit hydration is still debatable, despite the successful cases that have been presented in the last years. Indeed, how to select the water molecules that will be included in the docking process or how the included waters should be treated remain open questions. Objective: In this review, we will discuss some of the most recent methods that can be used in computational drug discovery and drug development when the effect of a single water, or of a small network of interacting waters, needs to be explicitly considered. Results: Here, we analyse the software to aid the selection, or to predict the position, of water molecules that are going to be explicitly considered in later docking studies. We also present software and protocols able to efficiently treat flexible water molecules during docking, including examples of applications. Finally, we discuss methods based on molecular dynamics simulations that can be used to integrate docking studies or to reliably and efficiently compute binding energies of ligands in presence of interfacial or bridging water molecules. Conclusions: Software applications aiding the design of new drugs that exploit water molecules, either as displaceable residues or as bridges to the receptor, are constantly being developed. Although further validation is needed, workflows that explicitly consider water will probably become a standard for computational drug discovery soon.

17

Patel, M. J., and R. J. Kassner. "Alkyl and aromatic isocyanide binding to haem complexes." Biochemical Journal 262, no. 3 (September 15, 1989): 959–63. http://dx.doi.org/10.1042/bj2620959.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

Equilibrium constants for the binding of ethyl (EIC), n-butyl (BIC), p-toluenesulphonylmethyl (TMIC) and 2,6-dimethylphenyl isocyanides (DIMPI) to an imidazole-haem complex in toluene and aqueous detergent micelle solutions were determined. In contrast to an earlier study, which indicated that the large affinities of myoglobin for binding DIMPI and 2,6-diethylphenylisocyanide (DEPI) relative to EIC were due to an electronic effect, the present study shows a similarity in binding constants for EIC, BIC, and DIMPI to the imidazole-haem complex in toluene, suggesting no such electronic effect is present. The measured hydrophobic effect (KDIMPI/KEIC = 11) cannot account for the large binding constant reported for DIMPI relative to the binding of EIC to myoglobin. Based on the results of these model studies, the equilibrium binding constant for DIMPI to myoglobin has been re-measured and the standard free energy of binding has been analysed by a more recent method.

18

Arshad, Nasima, Naghmana Rashid, Sajida Absar, Muhammad Abbasi, Samreen Saleem, and Bushra Mirza. "UV-absorption studies of interaction of karanjin and karanjachromene with ds. DNA: Evaluation of binding and antioxidant activity." Open Chemistry 11, no. 12 (December 1, 2013): 2040–47. http://dx.doi.org/10.2478/s11532-013-0327-z.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

AbstractTwo flavonoids, karanjin (Kj) and karanjachromene (Kc) have been investigated spectrophotometrically for their mode of interactions with double stranded (ds)-DNA at blood (7.4) and stomach (4.7) pH and at human body temperature (37°C). Benesi-Hildebrand equation was used to evaluate the binding constants, K b . Binding constants at both pH values and at body temperature showed stronger binding of both the flavonoids and formation of 1:1 flavonoid-DNA complex via intercalative mode. However, K b values for karanjin were evaluated to be comparatively greater than karanjachromene at both pH values. The highest value of binding constant (1.32×105 M−1) for karanjin at blood pH (7.4) demonstrated its comparatively stronger binding and greater effectiveness at this pH. Standard Gibbs free energy changes (ΔG) of flavonoid-DNA complexes were calculated as negative values and indicative of spontaneity of their binding. Both flavonoids showed significant DNA protection activity.

19

Gandhimathi, R., and S. Anbuselvi. "In silico Molecular Docking, ADMET Property, Molecular Dynamic Simulation Evaluation of N,N′-bis(2-Hydroxybenzylidene)-1,2-diaminobenzene and its Metal Complexes against SARS-CoV-2." Asian Journal of Chemistry 34, no. 10 (2022): 2573–82. http://dx.doi.org/10.14233/ajchem.2022.23883.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

In search of potent inhibitors of SARS-CoV-2, well familiar N,N′-bis(2-hydroxybenzylidene)-1,2- diaminobenzene [HBDB]/salophen ligand and its corresponding metal complexes such as [VO(HBDB)], [Mo(O)2(HBDB)], [W(O)2(HBDB)], [Fe(H2O)2(HBDB)], [Pb(H2O)2(HBDB)], [Sn(Cl)2(HBDB)] have been accompanied with standard drug hydroxychloroquine employing CADD tools such as the molecular docking, ADMET toxicity assessment and molecular dynamics of the coronavirus main protease (PDB id: 6LZG) enzyme. The synthesized salophen metal complexes exhibited the greater binding energy than corresponding salophen Schiff base ligand and standard hydroxychloroquine drug. Consequently, salophen metal complexes could serve as potential lead molecules against COVID-19 for further optimization and drug development to combat the virulent SARS-CoV-2 syndrome. The molecular dynamic simulation studies for [Mo(O2)(HBDB)] complex shows an excellent binding free energy about -170.833 Kcal/mol. Subsequently, it is confirmed that salophen metal complexes could serve as potential drugs against COVID-19 for further optimization and drug development to combat the virulent SARS-CoV-2 syndrome.

20

Boutarfaia, Amira, Lazhar Bechki, Touhami Lanez, Elhafnaoui Lanez, and Mohamed Kadri. "Synthesis, Antioxidant Activity, and Determination of Binding Parameters of Meso-Tetra-4-Actophenyl-Porphyrin and its Palladium (II) Complex with Superoxide Anion Radicals." Current Bioactive Compounds 16, no. 7 (October 28, 2020): 1063–71. http://dx.doi.org/10.2174/1573407215666191017105239.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

Background: Meso-tetra-4-actophenyl-porphyrin (TAcPPH2) was synthesized by reacting 4- acetyl-benzaldehyde with pyrrole in propionic acid, and used as a ligand for the synthesis of palladium (II) complex (PdTAcPP). The structure of the ligand and the complex were characterized by NMR and electronic spectroscopy. Methods: he antioxidant activity and the binding parameters of both the ligand and its complex with superoxide anion radical . (O2 -) were measured using cyclic voltammetry based assay. The assays were based on the measurement of the anodic peak current density of . O2− electrochemically generated by reduction of molecular oxygen in DMF. Results: The complex PdTAcPP showed the highest antioxidant activity (0.73 ± 0.01 mg/mL) which is four times higher than that of the standard antioxidant α-tocopherol (3.04 ± 0.03 mg/mL). Discussion: Binding parameters like binding constants, the ratio of binding constants and binding free energies were also measured. Conclusion: The value of the binding free energy ranging from -7.89 kJmol-1 for TAcPPH2 to -17.59 kJ.mol-1for PdTAcPP suggests an electrostatic interaction of . O2− with TAcPPH2 and PdTAcPP which has been found to be the dominant interaction mode. The kinetics of the interaction reaction of the ligand and complex was quantified having second-order rate constant values equal to 0.2 and 1.3 M-1 s-1, respectively.

21

Douadi, Khaoula, and Ilhem Kaabi. "Superoxide Anion Radical Interaction With New Quinoline Compounds Measured By Cyclic Voltammetry." Journal of Physical & Chemical Research 1, no. 1 (June 1, 2022): 32–39. http://dx.doi.org/10.58452/jpcr.v1i1.29.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

Cyclic voltammetry was used to study the interaction of four quinoline∙ −derivatives with superoxide anion radical (O 2 ). This method is basedon the decrease of the anodic peak current of the superoxide anionradical O∙ 2 − generated electrochemically by the reduction of molecularoxygen O2 dissolved in acetonitrile. The results obtained reveal that allderivatives showed a higher antioxidant activity than the standard usedBHT. The binding parameters of the studied compounds wereestimated in terms of binding constant (kb ), ratio of Binding Constants(K Red ⁄K Ox ) and binding Gibbs free energy (ΔG°). From the results, itappears that the binding constant kb of the tested compounds is veryhigh ranged from 15922 to 26181 L.mol-1 while negative values of ΔG°indicate the spontaneity of the antiradical reaction. It was also foundthat interaction of the reduced form O∙ 2 − with all derivatives is strongerthan the oxidized form O2 with ratio of binding constants values in therange 1.21-159.

22

Khan, Huma, Varun Jaiswal, Saurabh Kulshreshtha, and Azhar Khan. "Potential Angiotensin Converting Enzyme Inhibitors from Moringa oleifera." Recent Patents on Biotechnology 13, no. 3 (August 6, 2019): 239–48. http://dx.doi.org/10.2174/1872208313666190211114229.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

Background: Hypertension is the chronic medical condition and it affected billions of people worldwide. Natural medicines are the main alternatives to treatment for a majority of people suffering from hypertension. Niazicin-A, Niazimin-A, and Niaziminin-B compounds from Moringa oleifera ethanolic leave extract were reported to have potent antihypertensive activity. Objective: These compounds were targeted with Angiotensin-converting enzyme [ACE] which is one of the main regulatory enzymes of the renin-angiotensin system. Methods: Protein-ligand docking of these compounds with [ACE] [both domain N and C] was conceded out through Autodock vina and visualization was done by chimera. Pharmacokinetics study of these compounds was predicted by ADME-Toxicity Prediction. Results: Niazicin-A, Niazimin-A, and Niaziminin-B showed high binding affinity with ACE and partially blocked the active sites of the enzyme. Niazicin-A, Niazimin-A and Niaziminin-B showed the estimated free binding energy of -7.6kcal/mol kcal/mol, -8.8kcal/mol and -8.0kcal/mol respectively with C-domain of ACE and -7.9kcal/mol, -8.5kcal/mol and -7.7kcal/mol respectively with N-domain of ACE. The compounds showed better binding energy with angiotensinconverting enzyme in comparison to Captopril -5.5kcal/mol and -5.6kcal/mol and Enalapril [standard] -8.4kcal/mol and -7.5kcal/mol with C and N domain, respectively. Conclusion: Computationally, the selected bioactive molecules have shown better binding energy to known standard drugs which have been already known for inhibition of ACE and can further act as a pharmacophore for in vitro and in vivo studies in the development of alternative medicine.

23

Jubie, S., R. Kalirajan, and Pavankumar Yadav. "Design, Synthesis and Docking Studies of a Novel Ciprofloxacin Analogue as an Antimicrobial AGENT." E-Journal of Chemistry 9, no. 2 (2012): 980–87. http://dx.doi.org/10.1155/2012/340451.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

The carboxylic acid group of ciprofloxacin was modified and amino mercapto triazole was substituted. The compound was confirmed by physical parameters (solubility, melting point), chromatographic methods (TLC) and consistent with its IR &1HNMR spectra. The synthesized analogue was screened for antibacterial activity against one gram positive & two gram negative species. The compound exhibited good antibacterial effect towards gram negative species when compared to the standard ciprofloxacin. At the same time the analogue was retaining antibacterial activity towards gram positive species when compared to standard ciprofloxacin. The molecular docking studies showed a good correlation between their antibacterial activity and autodock binding free energy.

24

Poli, Giulio, Carlotta Granchi, Flavio Rizzolio, and Tiziano Tuccinardi. "Application of MM-PBSA Methods in Virtual Screening." Molecules 25, no. 8 (April 23, 2020): 1971. http://dx.doi.org/10.3390/molecules25081971.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

Computer-aided drug design techniques are today largely applied in medicinal chemistry. In particular, receptor-based virtual screening (VS) studies, in which molecular docking represents the gold standard in silico approach, constitute a powerful strategy for identifying novel hit compounds active against the desired target receptor. Nevertheless, the need for improving the ability of docking in discriminating true active ligands from inactive compounds, thus boosting VS hit rates, is still pressing. In this context, the use of binding free energy evaluation approaches can represent a profitable tool for rescoring ligand-protein complexes predicted by docking based on more reliable estimations of ligand-protein binding affinities than those obtained with simple scoring functions. In the present review, we focused our attention on the Molecular Mechanics-Poisson Boltzman Surface Area (MM-PBSA) method for the calculation of binding free energies and its application in VS studies. We provided examples of successful applications of this method in VS campaigns and evaluation studies in which the reliability of this approach has been assessed, thus providing useful guidelines for employing this approach in VS.

25

Gaikwad, Nikita Maruti, Pravin Digambar Chaudhari, Karimunnisa Sameer Shaikh, Somdatta Yashwant Chaudhari, Rasha Mohammed Saleem, Mohammad Algahtani, Ahmed E. Altyar, Ghadeer M. Albadrani, Mohamed Kamel, and Mohamed M. Abdel-Daim. "Albendazole repurposing on VEGFR-2 for possible anticancer application: In-silico analysis." PLOS ONE 18, no. 8 (August 16, 2023): e0287198. http://dx.doi.org/10.1371/journal.pone.0287198.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

Drug repurposing is the finding new activity of the existing drug. Recently, Albendazole’s well-known antihelmintic has got the attention of an anticancer drug. Plausible evidence of the interaction of Albendazole with one of the types of tyrosine kinase protein receptor, vascular endothelial growth factor receptor-2 (VEGFR-2) is still not well understood. Inhibition of the VEGFR-2 receptor can prevent tumor growth. The current study investigated the interaction of Albendazole with VEGFR-2.It was found that the said interaction exhibited potent binding energy ΔG = -7.12 kcal/mol, inhibitory concentration (Ki) = 6.04 μM, and as positive control comparison with standard drug (42Q1170A) showed ΔG = -12.35 kcal/mol and Ki = 881 μM. The key residue Asp1046 was formed involved hydrogen bonding with Albendazole. The molecular dynamics simulation study revealed the stable trajectory of the VEGFR-2 receptor with Albendazole bound complex having significant high free energy of binding as calculated from Molecular Mechanics Generalized Born and Surface Area study ΔG = -42.07±2.4 kcal/mol. The binding energy is significantly high for greater stability of the complex. Principal component analysis of molecular docking trajectories exhibited ordered motion at higher modes, implying a high degree of VEGFR-2 and Albendazole complex stability as seen with the standard drug 42Q. Therefore, the current work suggests the role of Albendazole as a potent angiogenesis inhibitor as ascertained by its potential interaction with VEGFR-2. The findings of research will aid in the future development of Albendazole in anticancer therapy.

26

Weigel, H., M. Quandt, and N. Graham. "Quantum stabilization of cosmic strings." Modern Physics Letters A 30, no. 27 (August 13, 2015): 1530022. http://dx.doi.org/10.1142/s0217732315300220.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

In the standard model, stabilization of a classically unstable cosmic string may occur through the quantum fluctuations of a heavy fermion doublet. We review numerical results from a semiclassical expansion in a reduced version of the standard model. In this expansion, the leading quantum corrections emerge at one loop level for many internal degrees of freedom. The resulting vacuum polarization energy and the binding energies of occupied fermion energy levels are of the same order, and must therefore be treated on equal footing. Populating these bound states lowers the total energy compared to the same number of free fermions and assigns a charge to the string. Charged strings are already stabilized for a fermion mass only somewhat larger than the top quark mass. Though obtained in a reduced version, these results suggest that neither extraordinarily large fermion masses nor unrealistic couplings are required to bind a cosmic string in the standard model. Furthermore, we also review results for a quantum stabilization mechanism that prevents closed Nielsen–Olesen-type strings from collapsing.

27

Morsy, Mohamed A., Snehal S. Patel, Anita Bakrania, Mahmoud Kandeel, Anroop B. Nair, Jigar N. Shah, Sabah H. Akrawi, and Mahmoud El-Daly. "Ameliorative Effect of a Neoteric Regimen of Catechin plus Cetirizine on Ovalbumin-Induced Allergic Rhinitis in Rats." Life 12, no. 6 (May 31, 2022): 820. http://dx.doi.org/10.3390/life12060820.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

Allergic rhinitis (AR) affects 20–50% of the global population. Available treatments are limited by their adverse effects. We investigated the anti-allergic effects of catechin alone and combined with cetirizine against ovalbumin-induced AR. Rats were sensitized with ovalbumin and received catechin (14 days) and then challenged with aerosolized ovalbumin (1%) to determine AR clinical scores. Histamine, histamine release, and histidine decarboxylase (HDC) activity were determined in blood, peritoneal mast cells, and stomachs, respectively. Vascular permeability and safety were assessed using Evans blue leakage and barbiturate-induced sleeping-time assays, respectively. Catechin and cetirizine binding with HDC was investigated by docking and binding energy analyses. The clinical scores of the combination regimen were superior to either drug alone. All treatments reduced vascular leakage, with no effect on barbiturate-induced sleeping time. Only the catechin-treated rats showed reduced histamine levels and HDC activity. Docking studies revealed that catechin has a 1.34-fold higher extra-precision docking score than L-histidine. The binding energy scores for catechin-HDC, L-histidine-HDC, and histamine-HDC were −50.86, −37.64, and −32.27 kcal/mol, respectively. The binding pattern of catechin was comparable to the standard HDC inhibitor, histidine methyl ester, but with higher binding free energy. Catechin binds the catalytic residue S354, unlike cetirizine. The anti-allergic effects of catechin can be explained by HDC inhibition and possible antihistaminic activity.

28

VENTURINO, ANDRÉS, ROSA MARÍA BERGOC, ANA MARÍA PECHEN DE D'ANGELO, and ENRIQUE ARTURO ROSENBAUM. "KINETIC MODELS ON ACETYLCHOLINESTERASE MODULATION BY SELF-SUBSTRATE AND POLYAMINES: ESTIMATION OF INTERACTION PARAMETERS AND RATE CONSTANTS FOR FREE AND ACETYLATED STATES OF THE ENZYME." Journal of Biological Systems 10, no. 02 (June 2002): 127–47. http://dx.doi.org/10.1142/s0218339002000470.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

Polyamines act as dual modulators on electric eel acetylcholinesterase, modifying both the apparent Km and Ki, depending on substrate levels. A kinetic model was developed to explain the results, based on two-step catalysis, a peripheral site for substrate inhibition apart from the catalytic site, and one binding site for polyamine. This model presented the best fittings to data, when compared with a simpler one considering one catalytic step. A fitting equation built up with sixteen independent parameters let us calculate the kinetic constants. In this way, we were able to solve the parameter identifiability problem arising from model uncertainty when only substrate was used in acetylcholinesterase kinetics. Besides, fitting parameters directly provide information about the binding constants of the different complexes, the modulatory strength of substrate and polyamines, and the effect on the standard activation free energy for acetylcholinesterase. Substrate inhibition operates mainly on the first catalytic step with an affinity constant of 5.2 mM-1, which is reduced to one third for the acetylated enzyme. The interaction factor between substrate binding at both sites is about 12. The modulatory strength of polyamines is spermine > spermidine > putrescine. This order is directly related to the number of amino groups in the molecule, and to the calculated free interaction energy. The effect of the number of amino groups on the binding energy is significantly increased in acetylated acetylcholinesterase. It is also inferred that the formation of a quaternary complex enzyme-substrate-substrate-polyamine would not be possible. Some relations between polyamine structure and acetylcholinesterase activity are suggested from estimated constants. Due to the distal amino group distances, it is possible for spermine and spermidine to span along the catalytic gorge of acetylcholinesterase, binding to the catalytic and peripheral sites in a way similar to bisquaternary ammonium inhibitors.

29

Devi, Sushma, Ankita Sharma, Veeresh Karoshi, Sunil Kumar, Ajay Kumar, and Jayant Sindhu. "Metal-Free Synthesis of 2-Aminothiazole Functionalized Imidazo[1,2-a]pyridines as Antibacterial Agents." INDIAN JOURNAL OF HETEROCYCLIC CHEMISTRY 34, no. 01 (March 2024): 23. http://dx.doi.org/10.59467/ijhc.2024.34.23.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

The present work describes the synthesis, characterization, and in silico studies of some new 2-aminothiazole functionalized imidazo[1,2-a]pyridines (1a-h). The targeted compounds were synthesized by the Hantzsch?s thiazole reaction involving the condensation reaction of a-bromomethyl ketones with 1-(3-nitroimidazo[1,2-a]pyridin-2-yl)thiourea (2). The key precursor 2 was synthesized by four steps method using 2-aminopyridine and chloroacetic acid as commercially available starting materials. The synthesized compounds 1a-1h displayed considerable activity against Gram-positive bacteria. In particular, compound 1b (R=2,4-dichloro) and 1e (R=4-carbethoxy) exhibited significant activity against Staphylococcus aureus and Bacillus subtilis in comparison to the standard antibacterial drug Ampicillin. The molecular docking and DFT studies of synthesized compounds were used to study the binding modes of these compounds. The compounds showed excellent binding energy scores (-8.3 to -9.3 kcal/mol) when interacting 1KZN protein (Escherichia coli) with compounds were examined which are in agreement with in vivo antibacterial activity.. KEYWORDS :a-Bromomethyl ketones, DFT studies, Escherichia coli, Imidazo[1,2-a]pyridines, Molecular docking.

30

Okoh, Olayinka Sunday, AbdulbasitHaliru Yakubu, Abayomi Emmanuel Adegboyega, Daniel Ejim Uti, Uket Nta Obeten, Samuel Ali Agada, Folusho Oluwaloni, et al. "Identification of some bioactive compounds from Trignonella foenumgraecum as possible inhibitors of PPARϒ for diabetes treatment through molecular docking studies, pharmacophore modelling and ADMET profiling: An in-silico study." PLOS ONE 18, no. 5 (May 18, 2023): e0284210. http://dx.doi.org/10.1371/journal.pone.0284210.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

Oral antidiabetic agents including the peroxisome proliferator-activated receptor gamma (PPARγ) agonists are available for the clinical management of diabetes mellitus (DM) but most are characterized by many adverse effects. In this study, we explore the antidiabetic properties of phytoconstituents from Trigonellafeonumgraecum (Fabaceae) as potential agonist of PPARγ; using in silico molecular docking, molecular mechanics generalized surface area (MM/GBSA)free binding energy prediction, Pharmacophore modeling experiment, and Pharmacokinetic/ toxicity analysis. One hundred and forty (140) compounds derived from Trigonellafeonumgraecum were screened by molecular docking against protein target PDB 3VI8. Results obtained from binding affinity (BA) and that of binding free energy (BFE) revealed five 5 compounds; arachidonic acid (CID_10467, BA -10.029, BFE -58.9), isoquercetin (CID_5280804, BA -9.507kcal/mol, BFE -56.33), rutin (CID_5280805, BA -9.463kcal/mol, BFE -56.33), quercetin (CID_10121947, BA -11.945kcal/mol, BFE -45.89) and (2S)-2-[[4-methoxy-3-[(pyrene-1-carbonylamino)methyl]phenyl]methyl]butanoic acid (CID_25112371, BA -10.679kcal/mol, BFE -45.73); and were superior to the standard; Rosiglitazone with a docking score of -7.672. Hydrogen bonding was notable in the protein-ligand complex interaction, with hydrophobic bond, polar bond and pipi stacking also observed. Their Pharmacokinetic/ toxicity profile showed varying druggable characteristics, but; arachidonic acid had the most favorable characteristics. These compounds are potential agonists of PPARγ and are considered as antidiabetic agents after successful experimental validation.

31

Manish Devgun, Sushil Prasad, SukhbirLal Khokra, and Rakesh Narang. "Molecular docking studies of dihydropyridazin-3(2H)-one derivatives as Antifungal, antibacterial and anti-helmintic agents." World Journal of Advanced Research and Reviews 12, no. 1 (October 30, 2021): 186–214. http://dx.doi.org/10.30574/wjarr.2021.12.1.0476.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

Molecular docking is the identification of ligand’s correct binding geometry i.e pose in the binding site and estimation of its binding affinity for the rational design of drug molecule. The current study endeavored the high throughput insilico screening of 24 compounds docked with their respective protein using PyRx-Virtual Screening Tool software. Out of 24 compounds, almost all test compounds showed a very good binding affinity score. Fluconazole was used as a standard drug in case of Antifungal, Ciprofloxacin in case of Antibacterial, and Albendazole in case of Antihelmintics. More negative is the binding free energy score, more favorable is the pose for binding to protein active site. Based on H-bond interactions of these 24 compounds, Compounds 3a5, 3c3, 3d5, 3d6 were found to be the similar outcome for antifungal activity as fluconazole, Compound3a1 for antibacterial, and Compounds 3b5, 3d6 for the antihelmintic agent. Furthermore, the affinity of any small ligand molecules can be considered as an extraordinary tool in the field of drug design and offer imminent in future examination to build up potent antimicrobial agents.

32

Blazhynska, Marharyta. "Standard binding free-energy calculation of glycophorin a dimer in non-isotropic media sheds light on the transmembrane alpha-helices association mechanism." Biophysical Journal 122, no. 3 (February 2023): 198a. http://dx.doi.org/10.1016/j.bpj.2022.11.1205.

Full text

APA, Harvard, Vancouver, ISO, and other styles

33

Forouzesh, Negin, and Nikita Mishra. "An Effective MM/GBSA Protocol for Absolute Binding Free Energy Calculations: A Case Study on SARS-CoV-2 Spike Protein and the Human ACE2 Receptor." Molecules 26, no. 8 (April 20, 2021): 2383. http://dx.doi.org/10.3390/molecules26082383.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

The binding free energy calculation of protein–ligand complexes is necessary for research into virus–host interactions and the relevant applications in drug discovery. However, many current computational methods of such calculations are either inefficient or inaccurate in practice. Utilizing implicit solvent models in the molecular mechanics generalized Born surface area (MM/GBSA) framework allows for efficient calculations without significant loss of accuracy. Here, GBNSR6, a new flavor of the generalized Born model, is employed in the MM/GBSA framework for measuring the binding affinity between SARS-CoV-2 spike protein and the human ACE2 receptor. A computational protocol is developed based on the widely studied Ras–Raf complex, which has similar binding free energy to SARS-CoV-2/ACE2. Two options for representing the dielectric boundary of the complexes are evaluated: one based on the standard Bondi radii and the other based on a newly developed set of atomic radii (OPT1), optimized specifically for protein–ligand binding. Predictions based on the two radii sets provide upper and lower bounds on the experimental references: −14.7(ΔGbindBondi)<−10.6(ΔGbindExp.)<−4.1(ΔGbindOPT1) kcal/mol. The consensus estimates of the two bounds show quantitative agreement with the experiment values. This work also presents a novel truncation method and computational strategies for efficient entropy calculations with normal mode analysis. Interestingly, it is observed that a significant decrease in the number of snapshots does not affect the accuracy of entropy calculation, while it does lower computation time appreciably. The proposed MM/GBSA protocol can be used to study the binding mechanism of new variants of SARS-CoV-2, as well as other relevant structures.

34

Katz, Dana, Dan Sindhikara, Michael DiMattia, and Abba E. Leffler. "Potency-Enhancing Mutations of Gating Modifier Toxins for the Voltage-Gated Sodium Channel NaV1.7 Can Be Predicted Using Accurate Free-Energy Calculations." Toxins 13, no. 3 (March 7, 2021): 193. http://dx.doi.org/10.3390/toxins13030193.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

Gating modifier toxins (GMTs) isolated from venomous organisms such as Protoxin-II (ProTx-II) and Huwentoxin-IV (HwTx-IV) that inhibit the voltage-gated sodium channel NaV1.7 by binding to its voltage-sensing domain II (VSDII) have been extensively investigated as non-opioid analgesics. However, reliably predicting how a mutation to a GMT will affect its potency for NaV1.7 has been challenging. Here, we hypothesize that structure-based computational methods can be used to predict such changes. We employ free-energy perturbation (FEP), a physics-based simulation method for predicting the relative binding free energy (RBFE) between molecules, and the cryo electron microscopy (cryo-EM) structures of ProTx-II and HwTx-IV bound to VSDII of NaV1.7 to re-predict the relative potencies of forty-seven point mutants of these GMTs for NaV1.7. First, FEP predicted these relative potencies with an overall root mean square error (RMSE) of 1.0 ± 0.1 kcal/mol and an R2 value of 0.66, equivalent to experimental uncertainty and an improvement over the widely used molecular-mechanics/generalized born-surface area (MM-GB/SA) RBFE method that had an RMSE of 3.9 ± 0.8 kcal/mol. Second, inclusion of an explicit membrane model was needed for the GMTs to maintain stable binding poses during the FEP simulations. Third, MM-GB/SA and FEP were used to identify fifteen non-standard tryptophan mutants at ProTx-II[W24] predicted in silico to have a at least a 1 kcal/mol gain in potency. These predicted potency gains are likely due to the displacement of high-energy waters as identified by the WaterMap algorithm for calculating the positions and thermodynamic properties of water molecules in protein binding sites. Our results expand the domain of applicability of FEP and set the stage for its prospective use in biologics drug discovery programs involving GMTs and NaV1.7.

35

Martiz, Reshma Mary, Shashank M. Patil, Deepika Thirumalapura Hombegowda, Abdullah M. Shbeer, Taha Alqadi, Mohammed Al-Ghorbani, Ramith Ramu, and Ashwini Prasad. "Phyto-Computational Intervention of Diabetes Mellitus at Multiple Stages Using Isoeugenol from Ocimum tenuiflorum: A Combination of Pharmacokinetics and Molecular Modelling Approaches." Molecules 27, no. 19 (September 22, 2022): 6222. http://dx.doi.org/10.3390/molecules27196222.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

In the present study, the anti-diabetic potential of Ocimum tenuiflorum was investigated using computational techniques for α-glucosidase, α-amylase, aldose reductase, and glycation at multiple stages. It aimed to elucidate the mechanism by which phytocompounds of O. tenuiflorum treat diabetes mellitus using concepts of druglikeness and pharmacokinetics, molecular docking simulations, molecular dynamics simulations, and binding free energy studies. Isoeugenol is a phenylpropene, propenyl-substituted guaiacol found in the essential oils of plants. During molecular docking modelling, isoeugenol was found to inhibit all the target enzymes, with a higher binding efficiency than standard drugs. Furthermore, molecular dynamic experiments revealed that isoeugenol was more stable in the binding pockets than the standard drugs used. Since our aim was to discover a single lead molecule with a higher binding efficiency and stability, isoeugenol was selected. In this context, our study stands in contrast to other computational studies that report on more than one compound, making it difficult to offer further analyses. To summarize, we recommend isoeugenol as a potential widely employed lead inhibitor of α-glucosidase, α-amylase, aldose reductase, and glycation based on the results of our in silico studies, therefore revealing a novel phytocompound for the effective treatment of hyperglycemia and diabetes mellitus.

36

Salamanova, M. Sh. "Mortars on binding alkaline activation." Herald of Dagestan State Technical University. Technical Sciences 48, no. 4 (February 12, 2022): 178–86. http://dx.doi.org/10.21822/2073-6185-2021-48-4-178-186.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

Objective. The problems of the negative impact of the carbonate technology for the production of Portland cement are hotly discussed at many scientific sites and the world community is striving to create more environmentally friendly and less energy-intensive binders. The development of clinker-free technology will allow solving many problems of a global scale, and the use of recycled or substandard material will expand the raw material base and reduce the burden on the environment.Method. When designing formulations for building mortars, it is necessary to take into account the compliance with the requirements for all mortars in general, both for plastering and for masonry, finishing, repair, etc. The study of the compositions of mortars was carried out by standard methods using a verified and certified equipment. Result. The paper presents the results of many years of work on the development of building composites based on binders of alkaline activation. Grades of solutions M75 - 150 were obtained, with the mobility of the mortar mixture Pk 1-2, shelf life of 33-120 minutes, with high adhesive strength of 0.62- 0.71 MPa. Conclusion. The proposed mortar compositions will make it possible to perform plastering, masonry and repair work requiring quick setting, and with proper adherence to the proposed recipes and methods for making mortars, it will be possible to obtain high-quality and durable material.

37

Preciado, Lina, Jaime Pereañez, Ettayapuram Azhagiya Singam, and Jeffrey Comer. "Interactions between Triterpenes and a P-I Type Snake Venom Metalloproteinase: Molecular Simulations and Experiments." Toxins 10, no. 10 (September 28, 2018): 397. http://dx.doi.org/10.3390/toxins10100397.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

Small molecule inhibitors of snake venom metalloproteinases (SVMPs) could provide a means to rapidly halt the progression of local tissue damage following viperid snake envenomations. In this study, we examine the ability of candidate compounds based on a pentacyclic triterpene skeleton to inhibit SVMPs. We leverage molecular dynamics simulations to estimate the free energies of the candidate compounds for binding to BaP1, a P-I type SVMP, and compare these results with experimental assays of proteolytic activity inhibition in a homologous enzyme (Batx-I). Both simulation and experiment suggest that betulinic acid is the most active candidate, with the simulations predicting a standard binding free energy of Δ G ∘ = − 11.0 ± 1.4 kcal/mol. The simulations also reveal the atomic interactions that underlie binding between the triterpenic acids and BaP1, most notably the electrostatic interaction between carboxylate groups of the compounds and the zinc cofactor of BaP1. Together, our simulations and experiments suggest that occlusion of the S1 ′ subsite is essential for inhibition of proteolytic activity. While all active compounds make hydrophobic contacts in the S1 ′ site, β -boswellic acid, with its distinct carboxylate position, does not occlude the S1 ′ site in simulation and exhibits negligible activity in experiment.

38

Suhandi, Cecep, Petrus Putra Bagaskhara, Muchtaridi Muchtaridi, Raden Indah Puspita Syafitri, Salma Hasni Amalia, Alifia Bintang Azzahra, and Zahra Ganesya Citraloka. "In Silico Study of Compound Extract In Soursop Plant (Annona muricata) as Ace Inhibitor In Hypertension Disease." Indonesian Journal of Computational Biology (IJCB) 1, no. 1 (October 21, 2022): 7. http://dx.doi.org/10.24198/ijcb.v1i1.40533.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

Hypertension is one of the risk factors for cardiovascular disease that has become a serious global health problem. In terms of searching for active compounds that have the potential as antihypertensives, phytochemical studies on natural ingredients are continuously being carried out. One of them is soursop which is known to be able to lower blood pressure in people with hypertension. Alkaloids contained in soursop leaves can work as Angiotensin Converting Enzyme Inhibitor hat reduce ADH hormone secretion. This research was conducted to find out the antihypertensive potential of natural compounds in soursop leaves that interact with ACEI. The research was carried out in two steps, namely molecular anchoring and pharmacophore modeling. Based on the research that has been done, Anomuricine is the compound with the most potential interaction with ACEI with a Gibbs free energy of -9.13 kcal/mol and an inhibition constant of 202.83 uM. In addition, the Anomuricine compound has a lower binding energy than the standard ligand binding energy. Thus, it can be said that Anomuricine from soursop leaves (Annona muricata) has the potential as a lead compound.

39

Golding, E. M., W. E. Teague, and G. P. Dobson. "Adjustment of K' to varying pH and pMg for the creatine kinase, adenylate kinase and ATP hydrolysis equilibria permitting quantitative bioenergetic assessment." Journal of Experimental Biology 198, no. 8 (August 1, 1995): 1775–82. http://dx.doi.org/10.1242/jeb.198.8.1775.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

Physiologists and biochemists frequently ignore the importance of adjusting equilibrium constants to the ionic conditions of the cell prior to calculating a number of bioenergetic and kinetic parameters. The present study examines the effect of pH and free magnesium levels (free [Mg2+]) on the apparent equilibrium constants (K') of creatine kinase (ATP: creatine N-phosphotransferase; EC 2.7.3.2), adenylate kinase (ATP:AMP phosphotransferase; EC 2.7.4.3) and adenosinetriphosphatase (ATP phosphohydrolase; EC 3.6.1.3) reactions. We show how K' can be calculated using the equilibrium constant of a specified chemical reaction (Kref) and the appropriate acid-dissociation and Mg(2+)-binding constants at an ionic strength (I) of 0.25 mol l-1 and 38 degrees C. Substituting the experimentally determined intracellular pH and free [Mg2+] into the equation containing a known Kref and two variables, pH and free [Mg2+], enables K' to be calculated at the experimental ionic conditions. Knowledge of K' permits calculation of cytosolic phosphorylation ratio ([ATP]/[ADP][Pi]), cytosolic free [ADP], free [AMP], standard transformed Gibbs energy of formation (delta fG' degrees ATP) and the transformed Gibbs energy of the system (delta fG' ATP) for the biological system. Such information is vital for the quantification of organ and tissue bioenergetics under physiological and pathophysiological conditions.

40

Ge, Xiaoxia, and Benoît Roux. "Calculation of the standard binding free energy of sparsomycin to the ribosomal peptidyl-transferase P-site using molecular dynamics simulations with restraining potentials." Journal of Molecular Recognition 23, no. 2 (March 2010): 128–41. http://dx.doi.org/10.1002/jmr.996.

Full text

APA, Harvard, Vancouver, ISO, and other styles

41

Kumar, Sanjay, Leena H. Bajrai, Arwa A. Faizo, Aiah M. Khateb, Areej A. Alkhaldy, Rashmi Rana, Esam I. Azhar, and Vivek Dhar Dwivedi. "Pharmacophore-Model-Based Drug Repurposing for the Identification of the Potential Inhibitors Targeting the Allosteric Site in Dengue Virus NS5 RNA-Dependent RNA Polymerase." Viruses 14, no. 8 (August 20, 2022): 1827. http://dx.doi.org/10.3390/v14081827.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

Dengue virus (DENV) is the causative agent of DENV infection. To tackle DENV infection, the development of therapeutic molecules as direct-acting antivirals (DAAs) has been demonstrated as a truly effective approach. Among various DENV drug targets, non-structural protein 5 (NS5)—a highly conserved protein among the family Flaviviridae—carries the RNA-dependent RNA polymerase (DENVRdRp) domain at the C-terminal, and its “N-pocket” allosteric site is widely considered for anti-DENV drug development. Therefore, in this study, we developed a pharmacophore model by utilising 41 known inhibitors of the DENVRdRp domain, and performed model screening against the FDA’s approved drug database for drug repurposing against DENVRdRp. Herein, drugs complying with the pharmacophore hypothesis were further processed through standard-precision (SP) and extra-precision (XP) docking scores (DSs) and binding pose refinement based on MM/GBSA binding energy (BE) calculations. This resulted in the identification of four potential potent drugs: (i) desmopressin (DS: −10.52, BE: −69.77 kcal/mol), (ii) rutin (DS: −13.43, BE: −67.06 kcal/mol), (iii) lypressin (DS: −9.84, BE: −67.65 kcal/mol), and (iv) lanreotide (DS: −8.72, BE: −64.7 kcal/mol). The selected drugs exhibited relevant interactions with the allosteric N-pocket of DENVRdRp, including priming-loop and entry-point residues (i.e., R729, R737, K800, and E802). Furthermore, 100 ns explicit-solvent molecular dynamics simulations and end-point binding free energy assessments support the considerable stability and free energy of the selected drugs in the targeted allosteric pocket of DENVRdRp. Hence, these four drugs, repurposed as potent inhibitors of the allosteric site of DENVRdRp, are recommended for further validation using experimental assays.

42

Hilal, Tarek, Vera Puetter, Christiane Otto, Karsten Parczyk, and Benjamin Bader. "A Dual Estrogen Receptor TR-FRET Assay for Simultaneous Measurement of Steroid Site Binding and Coactivator Recruitment." Journal of Biomolecular Screening 15, no. 3 (February 11, 2010): 268–78. http://dx.doi.org/10.1177/1087057109359196.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

The human estrogen receptors (hER) are members of the nuclear hormone receptor (NHR) superfamily and represent important drug targets for the pharmaceutical industry. Initially, ligand binding assays were used to identify novel ligands using receptors purified from native tissues. With the advent of molecular cloning techniques, cell-based transactivation assays have been the gold standard for many years of drug discovery. With the elucidation of the structural mechanisms underlying the activation of NHRs, cell-free assays with purified receptors have become important tools to directly assess different binding sites (e.g., the hormone binding site or the cofactor binding site). The available cell-free assays have so far facilitated the study of one binding site at a time. With the introduction of Terbium (Tb3+)–based time-resolved fluorescence energy transfer (TR-FRET), it has become possible to measure 2 different interactions within 1 test tube in parallel. The authors have applied this technology to develop a dual readout system for the simultaneous monitoring of steroid hormone site binding and cofactor peptide recruitment. They took advantage of a commercially available fluorescent tracer as an indicator for classical steroid site binding and designed a novel peptide derived from the peroxisome proliferator-activated receptor gamma coactivator-1a (PGC1a) as an indicator for functional agonistic behavior of a test compound. The established assay is able to differentiate between agonists, antagonists, partial agonists, and compounds binding to the cofactor recruitment site. The IC50 values obtained for a number of reference compounds in the multiplexed assay are in concordance with published data. The simple 1-step mix-and-measure protocol gives excellent quality and robustness and can be miniaturized to 5-µL volume.

43

Journal, Baghdad Science. "Synthesis, Spectral Study and Theoretical Treatment of Some Mixing Ligand Complexes of Quinaldic Acid and 1, 10-Phenathroline." Baghdad Science Journal 13, no. 2 (June 5, 2016): 320–30. http://dx.doi.org/10.21123/bsj.13.2.320-330.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

Metal complexes of Cu (II), Fe (III) and Mn (II) with Quinaldic acid (L1) and 1, 10-Phenathroline (L2) are synthesized and characterized by standaral physic- chemical procedures (element analysis, metal analysis, FTIR, Uv-Vis, magnetic moment and conductometeric measurements). On the base of these studies, mononuclear and six coordinated octahedral geometry and nonelectrolyte of these complexes have been proposed. The standard heat of formation (?Hºf) and binding energy (?Eb) for the free ligands and their complexes are calculated by using the PM3 method at 273K of Hyperchem.-8 program. The complexes are more stable than their ligands. Moreover, the electrostatic potential of free ligands are measured to investigate the reactive site of the molecules, PM3 is used to evaluate the vibrational spectra of the free ligands, the frequencies are obtained approximately agreed with those values experimentally found; in addition, the calculation helps to assign clearly the most diagnostic bands .

44

Kakhar Umar, Abd, James H. Zothantluanga, Jittima Amie Luckanagul, Patanachai Limpikirati, and Sriwidodo Sriwidodo. "Structure-based computational screening of 470 natural quercetin derivatives for identification of SARS-CoV-2 M^pro inhibitor." PeerJ 11 (March 14, 2023): e14915. http://dx.doi.org/10.7717/peerj.14915.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

Coronavirus disease 2019 (COVID-19) is a global pandemic infecting the respiratory system through a notorious virus known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to viral mutations and the risk of drug resistance, it is crucial to identify new molecules having potential prophylactic or therapeutic effect against SARS-CoV-2 infection. In the present study, we aimed to identify a potential inhibitor of SARS-CoV-2 through virtual screening of a compound library of 470 quercetin derivatives by targeting the main protease—Mpro (PDB ID: 6LU7). The study was carried out with computational techniques such as molecular docking simulation studies (MDSS), molecular dynamics (MD) simulations, and molecular mechanics generalized Born surface area (MMGBSA) techniques. Among the natural derivatives, compound 382 (PubChem CID 65604) showed the best binding affinity to Mpro (−11.1 kcal/mol). Compound 382 interacted with LYS5, TYR126, GLN127, LYS137, ASP289, PHE291, ARG131, SER139, GLU288, and GLU290 of the Mpro protein. The SARS-CoV-2 Mpro-382 complex showed acceptable stability during the 100 ns MD simulations. The SARS-CoV-2 Mpro-382 complex also showed an MM-GBSA binding free energy value of -54.0 kcal/mol. The binding affinity, stability, and free energy results for 382 and Mpro were better than those of the native ligand and the standard inhibitors ledipasvir and cobicistat. The conclusion of our study was that compound 382 has the potential to inhibit SARS-Cov-2 Mpro. However, further investigations such as in-vitro assays are recommended to confirm its in-silico potency.

45

Ahmad, Varish, Ibrahim Alotibi, Anwar A. Alghamdi, Aftab Ahmad, Qazi Mohammad Sajid Jamal, and Supriya Srivastava. "Computational Approaches to Evaluate the Acetylcholinesterase Binding Interaction with Taxifolin for the Management of Alzheimer’s Disease." Molecules 29, no. 3 (January 31, 2024): 674. http://dx.doi.org/10.3390/molecules29030674.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are enzymes that break down and reduce the level of the neurotransmitter acetylcholine (ACh). This can cause a variety of cognitive and neurological problems, including Alzheimer’s disease. Taxifolin is a natural phytochemical generally found in yew tree bark and has significant pharmacological properties, such as being anti-cancer, anti-inflammatory, and antioxidant. The binding affinity and inhibitory potency of taxifolin to these enzymes were evaluated through molecular docking and molecular dynamics simulations followed by the MMPBSA approach, and the results were significant. Taxifolin’s affinity for binding to the AChE–taxifolin complex was −8.85 kcal/mol, with an inhibition constant of 326.70 nM. It was observed to interact through hydrogen bonds. In contrast, the BChE–taxifolin complex binding energy was observed to be −7.42 kcal/mol, and it was significantly nearly equal to the standard inhibitor donepezil. The molecular dynamics and simulation signified the observed interactions of taxifolin with the studied enzymes. The MMPBSA total free energy of binding for AChE–taxifolin was −24.34 kcal/mol, while BChE–taxifolin was −16.14 kcal/mol. The present research suggests that taxifolin has a strong ability to bind and inhibit AChE and BChE and could be used to manage neuron-associated problems; however, further research is required to explore taxifolin’s neurological therapeutic potential using animal models of Alzheimer’s disease.

46

Armstrong, David A., Arvi Rauk, and Dake Yu. "Structures, binding energies, and thermodynamic functions of NH4+, NH3•+, and their H2O complexes." Canadian Journal of Chemistry 71, no. 9 (September 1, 1993): 1368–77. http://dx.doi.org/10.1139/v93-177.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

Ab initio calculations are performed for [Formula: see text] and [Formula: see text] complexes for n = 0–5. For n = 0 and 1, the geometries of the complexes are optimized at the HF/6-31 + G* and MP2/6-31 + G* levels, and the energies are evaluated at the G2 level. For n = 2–5, the geometry optimizations and frequency calculations are carried out at the HF/6-31 + G* level, and the MP2/6-31 + G* energies are calculated at the HF optimized geometries. Basis set superposition errors are corrected by the Boys–Bernardi scheme at the HF/6-31 + G* level. The gas phase thermodynamic properties [Formula: see text] are evaluated as functions of temperature using standard statistical methods. Based on the calculated binding energies and the thermodynamic functions, the incremental changes in enthalpies and free energies, ΔHn and ΔGn, for the gas phase equilibria (H2O)n−1 M+ + H2O → (H2O)nM+ for M+ = NH4+ and NH3•+, are evaluated in comparison with the experimental data for [Formula: see text] the present results suggest conformations for the hydrated complexes observed in the experiments. The total free energy change for filling the first hydration shell is significantly more negative for NH3•+ than for NH4+.

47

Kalirajan, Rajagopal, Arumugasamy Pandiselvi, Byran Gowramma, and Pandiyan Balachandran. "In-silico Design, ADMET Screening, MM-GBSA Binding Free Energy of Some Novel Isoxazole Substituted 9-Anilinoacridines as HER2 Inhibitors Targeting Breast Cancer." Current Drug Research Reviews 11, no. 2 (December 10, 2019): 118–28. http://dx.doi.org/10.2174/2589977511666190912154817.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

Background: Human Epidermal development factor Receptor-2 (HER2) is a membrane tyrosine kinase which is overexpressed and gene amplified in human breast cancers. HER2 amplification and overexpression have been linked to important tumor cell proliferation and survival pathways for 20% of instances of breast cancer. 9-aminoacridines are significant DNA-intercalating agents because of their antiproliferative properties. Objective: Some novel isoxazole substituted 9-anilinoacridines(1a-z) were designed by in-silico technique for their HER2 inhibitory activity. Docking investigations of compounds 1a-z are performed against HER2 (PDB id-3PP0) by using Schrodinger suit 2016-2. Methods: Molecular docking study for the designed molecules 1a-z are performed by Glide module, in-silico ADMET screening by QikProp module and binding free energy by Prime-MMGBSA module of Schrodinger suit. The binding affinity of designed molecules 1a-z towards HER2 was chosen based on GLIDE score. Results: Many compounds showed good hydrophobic communications and hydrogen bonding associations to hinder HER2. The compounds 1a-z, aside from 1z have significant Glide scores in the scope of - 4.91 to - 10.59 when compared with the standard Ethacridine (- 4.23) and Tamoxifen (- 3.78). The in-silico ADMET properties are inside the suggested about drug likeness. MM-GBSA binding of the most intense inhibitor is positive. Conclusion: The outcomes reveal that this study provides evidence for the consideration of isoxazole substituted 9-aminoacridine derivatives as potential HER2 inhibitors. The compounds, 1s,x,v,a,j,r with significant Glide scores may produce significant anti breast cancer activity and further in vitro and in vivo investigations may prove their therapeutic potential.

48

Al-Fayez, Nourah, Hany Elsawy, Mohammed A. Mansour, Mohamad Akbar Ali, and Ibrahim Elghamry. "Synthesis, Anticancer, Antioxidant, Anti-inflammatory, Antimicrobial Activities, Molecular Docking, and DFT Studies of Sultams Derived from Saccharin." Molecules 27, no. 20 (October 20, 2022): 7104. http://dx.doi.org/10.3390/molecules27207104.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

A series of N-substituted saccharins namely 2-(1,1-dioxido-3-oxobenzo[d]isothiazol-2(3H)-yl) acetonitrile (2) and (alkyl 1,1-dioxido-3-oxobenzo[d]isothiazol-2(3H)-yl) acetate (3a–g) were synthesized, in moderate to excellent yields, from commercially available starting materials by two different approaches and their chemical structures were characterized by spectroscopic techniques (1H-NMR, 13C-NMR, IR, and MS). All the synthesized compounds were evaluated for their anti-inflammatory toward IL-6 and TNF-α, antioxidant, as well as their anticancer activities against hepatic cancer cells. In addition, their anti-fungal and antibacterial activities against both Gram-positive and Gram-negative bacteria were tested. All the tested compounds have exhibited excellent (3a, d, e) to moderate anti-inflammatory activity. Additionally, esters (3b, f) and nitrile (2) showed excellent antioxidant activity. Furthermore, ester 3f, with isopropyl ester, exhibited the highest cytotoxic activity compared to the other esters. Moreover, all compounds were evaluated as selective inhibitors of the human COX-1 enzyme using molecular docking by calculating the free energy of binding, inhibition constant, and other parameters to find out the binding affinity. The molecular study showed that esters (3d, f) and nitrile (2) revealed the highest binding affinities, hence enhancing the inhibition activity with the active site of the COX-1 enzyme. All the tested compounds have more negative Gibbs free, electrostatic, and total intermolecular energies than the standard inhibitor ASA. These results indicate that, all the tested sultams are potent anti-inflammatory drugs as compared to standard inhibitors. Finally, the chemical properties and the quantum factors of synthesized sultams were calculated based on density functional theory (DFT) to predict reactivity, and then correlated with the experimental data. Ester 3f showed the lowest ionization potential and lowest energy gap (Egap = 7.5691 eV), which was correlated with its cytotoxic activity. Furthermore, the spatial electron distribution of HOMO, LUMO were computed and it clearly indicates the electron donation ability of all the tested compounds.

49

K, Pavani, D. S. N. B. K. Prasanth, Murthy K. R. Shadakshara, Sheikh F. Ahmad, Ramanjaneyulu Seemaladinne, Mithun Rudrapal, and Praveen Kumar Pasala. "Citronellal as a Promising Candidate for Alzheimer’s Disease Treatment: A Comprehensive Study on In Silico and In Vivo Anti-Acetylcholine Esterase Activity." Metabolites 13, no. 11 (November 4, 2023): 1133. http://dx.doi.org/10.3390/metabo13111133.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

One of the primary therapeutic approaches for managing Alzheimer’s disease (AD) involves the modulation of Acetylcholine esterase (AChE) activity to elevate acetylcholine (ACh) levels inside the brain. The current study employed computational chemistry approaches to evaluate the inhibitory effects of CTN on AChE. The docking results showed that Citronellal (CTN) and standard Donepezil (DON) have a binding affinity of −6.5 and −9.2 Kcal/mol, respectively, towards AChE. Further studies using molecular dynamics (MD) simulations were carried out on these two compounds. Binding free energy calculations and ligand-protein binding patterns suggested that CTN has a binding affinity of −12.2078. In contrast, DON has a much stronger binding relationship of −47.9969, indicating that the standard DON has a much higher binding affinity than CTN for AChE. In an in vivo study, Alzheimer-type dementia was induced in mice by scopolamine (1.5 mg/kg/day i.p) for 14 days. CTN was administered (25 and 50 mg/kg. i.p) along with scopolamine (SCO) administration. DON (0.5 mg/kg orally) was used as a reference drug. CTN administration significantly improved the mice’s behavior as evaluated by the Morris water maze test, evident from decreased escape latency to 65.4%, and in the CPS test, apparent from reduced escape latency to 69.8% compared to the positive control mice. Moreover, CTN significantly increased the activities of antioxidant enzymes such as catalase and superoxide dismutase (SOD) compared to SCO. Furthermore, CTN administration significantly decreased SCO-induced elevated AChE levels in mice. These results were supported by histopathological and in silico molecular docking studies. CTN may be a potential antioxidant and neuroprotective supplement.

50

Khushal, Aneela, Umar Farooq, Sara Khan, Azhar Rasul, Tanveer A. Wani, Seema Zargar, Sohail Anjum Shahzad, Syed Majid Bukhari, and Nazeer Ahmad Khan. "Bioactivity-Guided Synthesis: In Silico and In Vitro Studies of β-Glucosidase Inhibitors to Cope with Hepatic Cytotoxicity." Molecules 28, no. 18 (September 9, 2023): 6548. http://dx.doi.org/10.3390/molecules28186548.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Abstract:

The major cause of hyperglycemia can generally be attributed to β-glucosidase as per its involvement in non-alcoholic fatty liver disease. This clinical condition leads to liver carcinoma (HepG2 cancer). The phthalimides and phthalamic acid classes possess inhibitory potential against glucosidase, forming the basis for designing new phthalimide and phthalamic acid analogs to test their ability as potent inhibitors of β-glucosidase. The study also covers in silico (molecular docking and MD simulations) and in vitro (β-glucosidase and HepG2 cancer cell line assays) analyses. The phthalimide and phthalamic acid derivatives were synthesized, followed by spectroscopic characterization. The mechanistic complexities associated with β-glucosidase inhibition were identified via the docking of the synthesized compounds inside the active site of the protein, and the results were analyzed in terms of the best binding energy and appropriate docking pose. The top-ranked compounds were subjected to extensive MD simulation studies to understand the mode of interaction of the synthesized compounds and binding energies, as well as the contribution of individual residues towards binding affinities. Lower RMSD/RMSF values were observed for 2c and 3c, respectively, in the active site, confirming more stabilized, ligand-bound complexes when compared to the free state. An anisotropic network model was used to unravel the role of loop fluctuation in the context of ligand binding and the dynamics that are distinct to the bound and free states, supported by a 3D surface plot. An in vitro study revealed that 1c (IC50 = 1.26 µM) is far better than standard acarbose (2.15 µM), confirming the potential of this compound against the target protein. Given the appreciable potential of the candidate compounds against β-glucosidase, the synthesized compounds were further tested for their cytotoxic activity against hepatic carcinoma on HepG2 cancer cell lines. The cytotoxicity profile of the synthesized compounds was performed against HepG2 cancer cell lines. The resultant IC50 value (0.048 µM) for 3c is better than the standard (thalidomide: IC50 0.053 µM). The results promise the hypothesis that the synthesized compounds might become potential drug candidates, given the fact that the β-glucosidase inhibition of 1c is 40% better than the standard, whereas compound 3c holds more anti-tumor activity (greater than 9%) against the HepG2 cell line than the known drug.

Journal articles on the topic 'Standard Binding Free Energy'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles