Journal articles: 'Molecuar dynamics and docking simulation'

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Naqvi, Ahmad Abu Turab, Taj Mohammad, Gulam Mustafa Hasan, and Md Imtaiyaz Hassan. "Advancements in Docking and Molecular Dynamics Simulations Towards Ligand-receptor Interactions and Structure-function Relationships." Current Topics in Medicinal Chemistry 18, no. 20 (December 31, 2018): 1755–68. http://dx.doi.org/10.2174/1568026618666181025114157.

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Protein-ligand interaction is an imperative subject in structure-based drug design and protein function prediction process. Molecular docking is a computational method which predicts the binding of a ligand molecule to the particular receptor. It predicts the binding pose, strength and binding affinity of the molecules using various scoring functions. Molecular docking and molecular dynamics simulations are widely used in combination to predict the binding modes, binding affinities and stability of different protein-ligand systems. With advancements in algorithms and computational power, molecular dynamics simulation is now a fundamental tool to investigative bio-molecular assemblies at atomic level. These methods in association with experimental support have been of great value in modern drug discovery and development. Nowadays, it has become an increasingly significant method in drug discovery process. In this review, we focus on protein-ligand interactions using molecular docking, virtual screening and molecular dynamics simulations. Here, we cover an overview of the available methods for molecular docking and molecular dynamics simulations, and their advancement and applications in the area of modern drug discovery. The available docking software and their advancement including application examples of different approaches for drug discovery are also discussed. We have also introduced the physicochemical foundations of molecular docking and simulations, mainly from the perception of bio-molecular interactions.

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李, 博. "Progress in Molecular Docking and Molecular Dynamics Simulation." Journal of Comparative Chemistry 03, no. 01 (2019): 1–10. http://dx.doi.org/10.12677/cc.2019.31001.

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Miyagawa, Hiroh, and Kunihiro Kitamura. "1P565 Molecular dynamics simulations of association and docking between an inhibitor and an enzyme.(27. Molecular dynamics simulation,Poster Session,Abstract,Meeting Program of EABS & BSJ 2006)." Seibutsu Butsuri 46, supplement2 (2006): S288. http://dx.doi.org/10.2142/biophys.46.s288_1.

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Meng, Fancui. "Molecular Dynamics Simulation of VEGFR2 with Sorafenib and Other Urea-Substituted Aryloxy Compounds." Journal of Theoretical Chemistry 2013 (December 4, 2013): 1–7. http://dx.doi.org/10.1155/2013/739574.

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The binding mode of sorafenib with VEGFR2 was studied using molecular docking and molecular dynamics method. The docking results show that sorafenib forms hydrogen bonds with Asp1046, Cys919, and Glu885 of VEGFR2 receptor. Molecular dynamics simulation suggests that the hydrogen bond involving Asp1046 is the most stable one, and it is almost preserved during all the MD simulation time. The hydrogen bond formed with Cys919 occurs frequently after 6 ns, while the bifurcated hydrogen bonds involving Glu885 occurs occasionally. Meantime, molecular dynamics simulations of VEGFR2 with 11 other urea-substituted aryloxy compounds have also been performed, and the results indicate that a potent VEGFR2 inhibitor should have lower interaction energy with VEGFR2 and create at least 2 hydrogen bonds with VEGFR2.

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Bathelt, Christine, Rolf Schmid, and Jürgen Pleiss. "Regioselectivity of CYP2B6: homology modeling, molecular dynamics simulation, docking." Journal of Molecular Modeling 8, no. 11 (November 1, 2002): 327–35. http://dx.doi.org/10.1007/s00894-002-0104-y.

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Kurniawan, Isman, Muhammad Salman Fareza, and Ponco Iswanto. "CoMFA, Molecular Docking and Molecular Dynamics Studies on Cycloguanil Analogues as Potent Antimalarial Agents." Indonesian Journal of Chemistry 21, no. 1 (September 14, 2020): 66. http://dx.doi.org/10.22146/ijc.52388.

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Malaria is a disease that commonly infects humans in many tropical areas. This disease becomes a serious problem because of the high resistance of Plasmodium parasite against the well-established antimalarial agents, such as Artemisinin. Hence, new potent compounds are urgently needed to resolve this resistance problem. In the present study, we investigated cycloguanil analogues as a potent antimalarial agent by utilizing several studies, i.e., comparative of molecular field analysis (CoMFA), molecular docking and molecular dynamics (MD) simulation. A CoMFA model with five partial least square regressions (PLSR) was developed to predict the pIC50 value of the compound by utilizing a data set of 42 cycloguanil analogues. From statistical analysis, we obtained the r2 values of the training and test sets that were 0.85 and 0.70, respectively, while q2 of the leave-one-out cross-validation was 0.77. The contour maps of the CoMFA model were also interpreted to analyze the structural requirement regarding electrostatic and steric factors. The most active compound (c33) and least active compound (c8) were picked for molecular docking and MD analysis. From the docking analysis, we found that the attached substituent on the backbone structure of cycloguanil gives a significant contribution to antimalarial activity. The results of the MD simulation confirm the stability of the binding pose obtained from the docking simulations.

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Khare, Noopur, Sanjiv Kumar Maheshwari, Syed Mohd Danish Rizvi, Hind Muteb Albadrani, Suliman A. Alsagaby, Wael Alturaiki, Danish Iqbal, et al. "Homology Modelling, Molecular Docking and Molecular Dynamics Simulation Studies of CALMH1 against Secondary Metabolites of Bauhinia variegata to Treat Alzheimer’s Disease." Brain Sciences 12, no. 6 (June 12, 2022): 770. http://dx.doi.org/10.3390/brainsci12060770.

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Calcium homeostasis modulator 1 (CALHM1) is a protein responsible for causing Alzheimer’s disease. In the absence of an experimentally designed protein molecule, homology modelling was performed. Through homology modelling, different CALHM1 models were generated and validated through Rampage. To carry out further in silico studies, through molecular docking and molecular dynamics simulation experiments, various flavonoids and alkaloids from Bauhinia variegata were utilised as inhibitors to target the protein (CALHM1). The sequence of CALHM1 was retrieved from UniProt and the secondary structure prediction of CALHM1 was done through CFSSP, GOR4, and SOPMA methods. The structure was identified through LOMETS, MUSTER, and MODELLER and finally, the structures were validated through Rampage. Bauhinia variegata plant was used to check the interaction of alkaloids and flavonoids against CALHM1. The protein and protein–ligand complex were also validated through molecular dynamics simulations studies. The model generated through MODELLER software with 6VAM A was used because this model predicted the best results in the Ramachandran plot. Further molecular docking was performed, quercetin was found to be the most appropriate candidate for the protein molecule with the minimum binding energy of −12.45 kcal/mol and their ADME properties were analysed through Molsoft and Molinspiration. Molecular dynamics simulations showed that CALHM1 and CALHM1–quercetin complex became stable at 2500 ps. It may be seen through the study that quercetin may act as a good inhibitor for treatment. With the help of an in silico study, it was easier to analyse the 3D structure of the protein, which may be scrutinized for the best-predicted model. Quercetin may work as a good inhibitor for treating Alzheimer’s disease, according to in silico research using molecular docking and molecular dynamics simulations, and future in vitro and in vivo analysis may confirm its effectiveness.

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Zaki, Magdi E. A., Sami A. Al-Hussain, Vijay H. Masand, Siddhartha Akasapu, Sumit O. Bajaj, Nahed N. E. El-Sayed, Arabinda Ghosh, and Israa Lewaa. "Identification of Anti-SARS-CoV-2 Compounds from Food Using QSAR-Based Virtual Screening, Molecular Docking, and Molecular Dynamics Simulation Analysis." Pharmaceuticals 14, no. 4 (April 13, 2021): 357. http://dx.doi.org/10.3390/ph14040357.

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Due to the genetic similarity between SARS-CoV-2 and SARS-CoV, the present work endeavored to derive a balanced Quantitative Structure−Activity Relationship (QSAR) model, molecular docking, and molecular dynamics (MD) simulation studies to identify novel molecules having inhibitory potential against the main protease (Mpro) of SARS-CoV-2. The QSAR analysis developed on multivariate GA–MLR (Genetic Algorithm–Multilinear Regression) model with acceptable statistical performance (R2 = 0.898, Q2loo = 0.859, etc.). QSAR analysis attributed the good correlation with different types of atoms like non-ring Carbons and Nitrogens, amide Nitrogen, sp2-hybridized Carbons, etc. Thus, the QSAR model has a good balance of qualitative and quantitative requirements (balanced QSAR model) and satisfies the Organisation for Economic Co-operation and Development (OECD) guidelines. After that, a QSAR-based virtual screening of 26,467 food compounds and 360 heterocyclic variants of molecule 1 (benzotriazole–indole hybrid molecule) helped to identify promising hits. Furthermore, the molecular docking and molecular dynamics (MD) simulations of Mpro with molecule 1 recognized the structural motifs with significant stability. Molecular docking and QSAR provided consensus and complementary results. The validated analyses are capable of optimizing a drug/lead candidate for better inhibitory activity against the main protease of SARS-CoV-2.

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De Paris, Renata, Christian V. Quevedo, Duncan D. Ruiz, Osmar Norberto de Souza, and Rodrigo C. Barros. "Clustering Molecular Dynamics Trajectories for Optimizing Docking Experiments." Computational Intelligence and Neuroscience 2015 (2015): 1–9. http://dx.doi.org/10.1155/2015/916240.

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Molecular dynamics simulations of protein receptors have become an attractive tool for rational drug discovery. However, the high computational cost of employing molecular dynamics trajectories in virtual screening of large repositories threats the feasibility of this task. Computational intelligence techniques have been applied in this context, with the ultimate goal of reducing the overall computational cost so the task can become feasible. Particularly, clustering algorithms have been widely used as a means to reduce the dimensionality of molecular dynamics trajectories. In this paper, we develop a novel methodology for clustering entire trajectories using structural features from the substrate-binding cavity of the receptor in order to optimize docking experiments on a cloud-based environment. The resulting partition was selected based on three clustering validity criteria, and it was further validated by analyzing the interactions between 20 ligands and a fully flexible receptor (FFR) model containing a 20 ns molecular dynamics simulation trajectory. Our proposed methodology shows that taking into account features of the substrate-binding cavity as input for thek-means algorithm is a promising technique for accurately selecting ensembles of representative structures tailored to a specific ligand.

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Luo, Lianxiang, Ai Zhong, Qu Wang, and Tongyu Zheng. "Structure-Based Pharmacophore Modeling, Virtual Screening, Molecular Docking, ADMET, and Molecular Dynamics (MD) Simulation of Potential Inhibitors of PD-L1 from the Library of Marine Natural Products." Marine Drugs 20, no. 1 (December 25, 2021): 29. http://dx.doi.org/10.3390/md20010029.

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Background: In the past decade, several antibodies directed against the PD-1/PD-L1 interaction have been approved. However, therapeutic antibodies also exhibit some shortcomings. Using small molecules to regulate the PD-1/PD-L1 pathway may be another way to mobilize the immune system to fight cancer. Method: 52,765 marine natural products were screened against PD-L1(PDBID: 6R3K). To identify natural compounds, a structure-based pharmacophore model was generated, following by virtual screening and molecular docking. Then, the absorption, distribution, metabolism, and excretion (ADME) test was carried out to select the most suitable compounds. Finally, molecular dynamics simulation was also performed to validate the binding property of the top compound. Results: Initially, 12 small marine molecules were screened based on the pharmacophore model. Then, two compounds were selected for further evaluation based on the molecular docking scores. After ADME and toxicity studies, molecule 51320 was selected for further verification. By molecular dynamics analysis, molecule 51320 maintains a stable conformation with the target protein, so it has the chance to become an inhibitor of PD-L1. Conclusions: Through structure-based pharmacophore modeling, virtual screening, molecular docking, ADMET approaches, and molecular dynamics (MD) simulation, the marine natural compound 51320 can be used as a small molecule inhibitor of PD-L1.

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Hung, Tzu-Chieh, Wen-Yuan Lee, Kuen-Bao Chen, Yueh-Chiu Chan, and Calvin Yu-Chian Chen. "Investigation of Estrogen Receptor (ESR1) for Breast Cancer from Traditional Chinese Medicine." BioMed Research International 2014 (2014): 1–12. http://dx.doi.org/10.1155/2014/321486.

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Recently, an important topic of breast cancer had been published in 2013. In this report, estrogen receptor (ESR1) had defined the relation of hormone-cause breast cancer. The screening of traditional Chinese medicine (TCM) database has found the molecular compounds by simulating molecular docking and molecular dynamics to regulate ESR1. S-Allylmercaptocysteine and 5-hydroxy-L-tryptophan are selected according to the highest docking score than that of other TCM compounds and Raloxifene (control). The simulation from molecular dynamics is helpful in analyzing and detecting the protein-ligand interactions. After a comparing the control and the Apo form, then based on the docking poses, hydrophobic interactions, hydrogen bond and structure variations, this research postulates that S-allylmercaptocysteine may be more appropriate than other compounds for protein-ligand interaction.

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Zhao, Yilan, Honghao Yang, Fengshou Wu, Xiaogang Luo, Qi Sun, Weiliang Feng, Xiulian Ju, and Genyan Liu. "Exploration of N-Arylsulfonyl-indole-2-carboxamide Derivatives as Novel Fructose-1,6-bisphosphatase Inhibitors by Molecular Simulation." International Journal of Molecular Sciences 23, no. 18 (September 6, 2022): 10259. http://dx.doi.org/10.3390/ijms231810259.

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A series of N-arylsulfonyl-indole-2-carboxamide derivatives have been identified as potent fructose-1,6-bisphosphatase (FBPase) inhibitors (FBPIs) with excellent selectivity for the potential therapy of type II diabetes mellitus. To explore the structure–activity relationships (SARs) and the mechanisms of action of these FBPIs, a systematic computational study was performed in the present study, including three-dimensional quantitative structure–activity relationship (3D-QSAR) modeling, pharmacophore modeling, molecular dynamics (MD), and virtual screening. The constructed 3D-QSAR models exhibited good predictive ability with reasonable parameters using comparative molecular field analysis (q2 = 0.709, R2 = 0.979, rpre2 = 0.932) and comparative molecular similarity indices analysis (q2 = 0.716, R2 = 0.978, rpre2 = 0.890). Twelve hit compounds were obtained by virtual screening using the best pharmacophore model in combination with molecular dockings. Three compounds with relatively higher docking scores and better ADME properties were then selected for further studies by docking and MD analyses. The docking results revealed that the amino acid residues Met18, Gly21, Gly26, Leu30, and Thr31 at the binding site were of great importance for the effective bindings of these FBPIs. The MD results indicated that the screened compounds VS01 and VS02 could bind with FBPase stably as its cognate ligand in dynamic conditions. This work identified several potential FBPIs by modeling studies and might provide important insights into developing novel FBPIs.

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Sahu, Satya Narayan, and Subrat Kumar Pattanayak. "Molecular docking and molecular dynamics simulation studies on PLCE1 encoded protein." Journal of Molecular Structure 1198 (December 2019): 126936. http://dx.doi.org/10.1016/j.molstruc.2019.126936.

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Takemura, Kazuhiro, Chika Sato, and Akio Kitao. "ColDock: Concentrated Ligand Docking with All-Atom Molecular Dynamics Simulation." Journal of Physical Chemistry B 122, no. 29 (July 11, 2018): 7191–200. http://dx.doi.org/10.1021/acs.jpcb.8b02756.

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Di Nola, Alfredo, Danilo Roccatano, and Herman J. C. Berendsen. "Molecular dynamics simulation of the docking of substrates to proteins." Proteins: Structure, Function, and Genetics 19, no. 3 (July 1994): 174–82. http://dx.doi.org/10.1002/prot.340190303.

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Luo, Lianxiang, Qu Wang, and Yinglin Liao. "The Inhibitors of CDK4/6 from a Library of Marine Compound Database: A Pharmacophore, ADMET, Molecular Docking and Molecular Dynamics Study." Marine Drugs 20, no. 5 (May 12, 2022): 319. http://dx.doi.org/10.3390/md20050319.

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Background: CDK4/6 (Cyclin-dependent kinases 4/6) are the key promoters of cell cycle transition from G1 phase to S phase. Thus, selective inhibition of CDK4/6 is a promising cancer treatment. Methods: A total of 52,765 marine natural products were screened for CDK4/6. To screen out better natural compounds, pharmacophore models were first generated, then the absorption, distribution, metabolism, elimination, and toxicity (ADMET) were tested, followed by molecular docking. Finally, molecular dynamics simulation was carried out to verify the binding characteristics of the selected compounds. Results: Eighty-seven marine small molecules were screened based on the pharmacophore model. Then, compounds 41369 and 50843 were selected according to the ADMET and molecular docking score for further kinetic simulation evaluation. Finally, through molecular dynamics analysis, it was confirmed that compound 50843 maintained a stable conformation with the target protein, so it has the opportunity to become an inhibitor of CDK4/6. Conclusion: Through structure-based pharmacophore modeling, ADMET, the molecular docking method and molecular dynamics (MD) simulation, marine natural compound 50843 was proposed as a promising marine inhibitor of CDK4/6.

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Kenneth Obiakor, Onyeka Chinwuba Obidiegwu, Keziah Uchechi Ajah, Christian Chidebe, Ajuzie Henry Ogechi, and Ikemefuna Chijioke Uzochukwu. "Discovery of antiadhesins of Helicobacter pylori from existing drugs and medicines for malaria ventures pathogen box compounds." GSC Biological and Pharmaceutical Sciences 20, no. 3 (September 30, 2022): 198–212. http://dx.doi.org/10.30574/gscbps.2022.20.3.0356.

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Background: Helicobacter pylori infection is a worldwide problem with more than half of the world's population in both developed and developing countries are infected with this organism. The best-characterized H. pylori adhesins, Blood group antigen binding Adhesin (BabA) and Sialic acid binding Adhesin (SabA) are virulent factors which facilitate adhesion of the bacteria to the host cells. Methods: We determined the binding affinities of selected existing drugs and medicines for malaria venture pathogen box compounds to H. pylori adhesin receptors by molecular docking simulations. The 3D crystal structures of H. pylori adhesin receptors were obtained from Protein Data Bank (PDB). The receptors were prepared for molecular docking simulations using PyMol 1.3, Chimera 1.9 and AutoDock tools 1.5.6. The 3D structures of the selected existing drugs and Medicines for Malaria Ventures (MMV) pathogen box compounds were obtained from ZINC and PubChem databases. They were prepared for molecular docking simulations using AutoDock tools 1.5.6. Docking protocols were validated by reproducing the PDB crystal structures in silico. Molecular docking simulations were executed with a virtual screening script using AutoDock Vina 1.1.2 on a Linux platform. Results: Entacapone, sildenafil, gemcitabine, tolcapone, rabeprazole, tolazamide, teriflunomide, sulfamethazine, cefotetan, talbutal, mitotane, tolbutamide, piperazine showed higher average binding affinities than the reference compound nitazoxanide molecular dynamics of one front runner with the reference ligand and protein were done at 1000 ps. Rabeprazole showed lower stability than the reference drug after molecular dynamics simulation. Conclusion: The identified existing drugs from molecular docking simulations with higher average binding affinities are predicted as possible H. pylori multi-target antiadhesins.

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Ifaya, Mus, Ida Musfiroh, Sahidin, Gofarana Wilar, Yasmiwar Susilawati, Syawal abdurrahman, and Dwi Syah Fitra Ramadhan. "MOLECULAR DOCKING AND DYNAMICS SIMULATIONS OF FENOLIC CONTENTS ON HENNA PLANT (Lawsonia inermis L.) AS ANTIDIBETIC THROUGH INHIBITION OF DIGESTIVE ENZYME α-AMYLASE." RASAYAN Journal of Chemistry 15, no. 02 (2022): 861–69. http://dx.doi.org/10.31788/rjc.2022.1526654.

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Diabetes mellitus is a disease caused by high blood glucose levels, and one way to overcome it is by inhibiting the digestive enzyme, α-amylase. The henna plant (Lawsonia inermis L.) has been shown to show potential as an antidiabetic through inhibition of the enzyme digestive, but its molecular mechanism has not been revealed. Therefore, the aim of this study was to reveal the α-amylase enzyme inhibitory activity of phenolic compounds in the henna plant by molecular docking and molecular dynamics. The protein used was a high-resolution α-amylase crystallographic protein with the code PDB: 1XD0, and the ligands used were 20 phenolic compounds that were known to be contained in the henna plant. The phenolic compounds were docking, then a molecular dynamic simulation was carried out, and then compared with acarbose. Molecular docking analysis shows 3 compounds with the best binding energies, e.g. Acacetin-7-o-glucoside, laxanthone-2, and laxanthone-3. Furthermore, tracing the stability of the three compounds using a molecular dynamics simulation based on the parameters of SASA, Rg, PCA, and MM-PBSA binding free energy, obtained good stability and is close to acarbose as reference ligand.

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Kumar, Anish. "STRUCTURAL AND FUNCTIONAL IMPACT OF G2032R MUTATION IN ROS1 – A THEORETICAL PERSPECTIVE." Asian Journal of Pharmaceutical and Clinical Research 10, no. 5 (May 1, 2017): 339. http://dx.doi.org/10.22159/ajpcr.2017.v10i5.17661.

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Objective: Drug resistance is an imperative issue in the treatment of patients with lung cancer. In this work, investigation of the drug resistance mechanism of G2032R mutation in ROS1 is carried out using computational simulation techniques.Methods: Molecular docking and molecular dynamics (MD) simulation approach have been utilized to uncover the mechanism behind crizotinib resistance in ROS1 at a molecular level. Normal mode analysis was carried out using ElNemo server which examines the movements and conformational changes in the protein structure. ArgusLab, PEARLS, and Autodock were employed for the docking analysis, whereas GROMACS package 4.5.3 was used for MD simulation approach.Results: The results from our analysis indicates that wild-type ROS1 (Protein Data Bank Code 3ZBF) could be more crucial for the crizotinib binding as it indicates largest binding affinity, minimum number of H-bonds, and higher flexibility than mutant-type ROS1. Moreover, the theoretical basis for the cause of drug insensitivity is the differences in the electrostatic properties of binding site residues between the wild and mutant ROS1 structures. Our analysis theoretically suggests that E-2027 is a key residue responsible for the ROS1 drug selectivity.Conclusion: Molecular docking and MD simulation results provide an explanation of the resistance caused by G2032R and may give a key clue for the drug design to encounter drug resistance.Keywords: ROS1, Crizotinib resistance, Molecular docking, Normal mode analysis, Molecular dynamic simulation.

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Seniya, Chandrabhan, Ghulam Jilani Khan, and Kuldeep Uchadia. "Identification of Potential Herbal Inhibitor of Acetylcholinesterase Associated Alzheimer’s Disorders Using Molecular Docking and Molecular Dynamics Simulation." Biochemistry Research International 2014 (2014): 1–7. http://dx.doi.org/10.1155/2014/705451.

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Cholinesterase inhibitors (ChE-Is) are the standard for the therapy of AD associated disorders and are the only class of approved drugs by the Food and Drug Administration (FDA). Additionally, acetylcholinesterase (AChE) is the target for many Alzheimer’s dementia drugs which block the function of AChE but have some side effects. Therefore, in this paper, an attempt was made to elucidate cholinesterase inhibition potential of secondary metabolite fromCannabisplant which has negligible or no side effect. Molecular docking of 500 herbal compounds, against AChE, was performed using Autodock 4.2 as per the standard protocols. Molecular dynamics simulations have also been carried out to check stability of binding complex in water for 1000 ps. Our molecular docking and simulation have predicted high binding affinity of secondary metabolite (C28H34N2O6) to AChE. Further, molecular dynamics simulations for 1000 ps suggest that ligand interaction with the residues Asp72, Tyr70-121-334, and Phe288 of AChE, all of which fall under active site/subsite or binding pocket, might be critical for the inhibitory activity of AChE. This approach might be helpful to understand the selectivity of the given drug molecule in the treatment of Alzheimer's disease. The study provides evidence for consideration ofC28H34N2O6as a valuable small ligand molecule in treatment and prevention of AD associated disorders and furtherin vitroandin vivoinvestigations may prove its therapeutic potential.

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Talarico, Carmine, Silvia Gervasoni, Candida Manelfi, Alessandro Pedretti, Giulio Vistoli, and Andrea R. Beccari. "Combining Molecular Dynamics and Docking Simulations to Develop Targeted Protocols for Performing Optimized Virtual Screening Campaigns on the hTRPM8 Channel." International Journal of Molecular Sciences 21, no. 7 (March 25, 2020): 2265. http://dx.doi.org/10.3390/ijms21072265.

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Background: There is an increasing interest in TRPM8 ligands of medicinal interest, the rational design of which can be nowadays supported by structure-based in silico studies based on the recently resolved TRPM8 structures. Methods: The study involves the generation of a reliable hTRPM8 homology model, the reliability of which was assessed by a 1.0 μs MD simulation which was also used to generate multiple receptor conformations for the following structure-based virtual screening (VS) campaigns; docking simulations utilized different programs and involved all monomers of the selected frames; the so computed docking scores were combined by consensus approaches based on the EFO algorithm. Results: The obtained models revealed very satisfactory performances; LiGen™ provided the best results among the tested docking programs; the combination of docking results from the four monomers elicited a markedly beneficial effect on the computed consensus models. Conclusions: The generated hTRPM8 model appears to be amenable for successful structure-based VS studies; cross-talk modulating effects between interacting monomers on the binding sites can be accounted for by combining docking simulations as performed on all the monomers; this strategy can have general applicability for docking simulations involving quaternary protein structures with multiple identical binding pockets.

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Pitaloka, Dian Ayu Eka, Sophi Damayanti, Aluicia Anita Artarini, and Elin Yulinah Sukandar. "Molecular Docking, Dynamics Simulation, and Scanning Electron Microscopy (SEM) Examination of Clinically Isolated Mycobacterium tuberculosis by Ursolic Acid: A Pentacyclic Triterpenes." Indonesian Journal of Chemistry 19, no. 2 (April 9, 2019): 328. http://dx.doi.org/10.22146/ijc.33731.

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The purpose of this study was to analyze the inhibitory action of ursolic acid (UA) as an antitubercular agent by computational docking studies and molecular dynamics simulations. The effect of UA on the cell wall of Mycobacterium tuberculosis (MTB) was evaluated by using Scanning Electron Microscopy (SEM). UA was used as a ligand for molecular interaction and investigate its binding activities to a group of proteins involved in the growth of MTB and the biosynthesis of the cell wall. Computational docking analysis was performed by using autodock 4.2.6 based on scoring functions. UA binding was confirmed by 30 ns molecular dynamics simulation using gromacs 5.1.1. H37Rv sensitive strain and isoniazid-resistant strain were used in the SEM study. UA showed to have the optimum binding affinity to inhA (Two-trans-enoyl-ACP reductase enzyme involved in elongation of fatty acid) with the binding energy of -9.2 kcal/mol. The dynamic simulation showed that the UA-inhA complex relatively stable and found to establish hydrogen bond with Thr196 and Ile194. SEM analysis confirms that UA treatment in both sensitive strain and resistant strain affected the morphology cell wall of MTB. This result indicated that UA could be one of the potential ligands for the development of new antituberculosis drugs.

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Milanović, Žiko, Dušan Dimić, Jasmina Dimitrić Marković, Marijana Stanojević-Pirković, Edina Avdović, and Zoran Marković. "THE INTERACTION OF PROTONATED OCTOPAMINE AND NOREPINEPHRINE WITH Β1-ADRENERGIC RECEPTOR: MOLECULAR DOCKING AND DYNAMICAL SIMULATION." Journal of the Serbian Society for Computational Mechanics, Special (June 1, 2020): 13–25. http://dx.doi.org/10.24874/jsscm.2020.01.02.

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In the current study, the interaction mechanisms between protonated neurotransmitters: octopamine (4-(2-amino-1-hydroxyethyl)phenol) and norepinephrine (4-[(1R)-2-amino-1-hydroxyethyl]benzene-1,2-diol) with the β-1 adrenergic receptor (β1AR) were examined by molecular docking, molecular dynamics (MD) simulations and MM/PBSA free energy calculations. The investigated receptor belongs to the G-protein coupled receptor group. The investigation was carried out at physiological pH=7.4. It was estimated that both compounds exist in the protonated form in the water at physiological pH. It was found that both protonated neurotransmitters established similar interactions with amino acid residues of the receptor, such as salt bridges, conventional hydrogen bonds, π-σ, and T-shaped π-π interactions, as shown by molecular docking simulations. As the initial structures for MD simulation with a total time of 10ns the most stable docking structures were used. The presented results are expected to provide some useful information for the design of specific β1AR agonists.

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Lu, Shao-Yong, Yong-Jun Jiang, Jing Lv, Tian-Xing Wu, Qing-Sen Yu, and Wei-Liang Zhu. "Molecular docking and molecular dynamics simulation studies of GPR40 receptor–agonist interactions." Journal of Molecular Graphics and Modelling 28, no. 8 (June 2010): 766–74. http://dx.doi.org/10.1016/j.jmgm.2010.02.001.

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Al-hussaniy, Hany Akeel. "The development of molecular docking and molecular dynamics and their application in the field of chemistry and computer simulation." Journal of medical pharmaceutical and allied sciences 12, no. 1 (January 31, 2023): 5552–62. http://dx.doi.org/10.55522/jmpas.v12i1.4137.

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With the rapid development of modern life science, computational Molecular docking has gradually become one of the core disciplines and methods of modern life science research. Computational docking studies the relationship between the structure and pharmacodynamics of biological macromolecules and the interaction between biological macromolecules and ligands. It promotes the development of protein engineering, protein design, and computer-aided drug design with powerful and various docking software in predicting the three-dimensional structure and dynamic characteristics of proteins from protein sequences. Nowadays, this computing power can be provided by the GPU through the use of a general-purpose computing model on GPUs. This article presents two approaches to parallelizing the descriptive algorithms on the GPU to solve the molecular docking problem and then evaluating them in terms of the computation time achieved. The proposed approaches are effective in accelerating molecular docking on GPUs compared to a single-core or multicore CPU. Besides introducing parallelization approaches, we propose a new descriptive algorithm based on the bee swarm algorithm to solve the molecular docking problem as an alternative to traditional descriptive algorithms such as the genetic algorithm.

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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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de Molfetta, Fábio Alberto, Renato Ferreira de Freitas, Albérico Borges Ferreira da Silva, and Carlos Alberto Montanari. "Docking and molecular dynamics simulation of quinone compounds with trypanocidal activity." Journal of Molecular Modeling 15, no. 10 (March 5, 2009): 1175–84. http://dx.doi.org/10.1007/s00894-009-0468-3.

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Kumaresan, J., T. Kothai, and B. S. Lakshmi. "In silicoapproaches towards understanding CALB using molecular dynamics simulation and docking." Molecular Simulation 37, no. 12 (October 2011): 1053–61. http://dx.doi.org/10.1080/08927022.2011.589050.

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Kumar, Rakesh, and Shweta Saran. "Structure, molecular dynamics simulation, and docking studies ofDictyostelium discoideumand human STRAPs." Journal of Cellular Biochemistry 119, no. 9 (May 24, 2018): 7177–91. http://dx.doi.org/10.1002/jcb.26840.

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Mukerjee, Nobendu, Anubhab Das, Swastika Maitra, Arabinda Ghosh, Prattusha Khan, Athanasios Alexiou, Abhijit Dey, et al. "Dynamics of natural product Lupenone as a potential fusion inhibitor against the spike complex of novel Semliki Forest Virus." PLOS ONE 17, no. 2 (February 25, 2022): e0263853. http://dx.doi.org/10.1371/journal.pone.0263853.

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The Semliki Forest Virus (SFV) is an RNA virus with a positive-strand that belongs to the Togaviridae family’s Alphavirus genus. An epidemic was observed among French troops stationed in the Central African Republic, most likely caused by the SFV virus. The two transmembrane proteins El and E2 and the peripheral protein E3 make up the viral spike protein. The virus binds to the host cell and is internalized via endocytosis; endosome acidification causes the E1/E2 heterodimer to dissociate and the E1 subunits to trimerize. Lupenone was evaluated against the E1 spike protein of SFV in this study based on state-of-the-art cheminformatics approaches, including molecular docking, molecular dynamics simulation, and binding free energy calculation. The molecular docking study envisaged major interactions of Lupenone with binding cavity residues involved non-bonded van der Waal’s and Pi-alkyl interactions. Molecular dynamic simulation of a time scale 200 ns corroborated interaction pattern with molecular docking studies between Lupenone and E1 spike protein. Nevertheless, Lupenone intearcation with the E1 spike protein conforming into a stable complex substantiated by free energy landscape (FEL), PCA analysis. Free energy decomposition of the binding cavity resdiues of E1 spike protein also ensured the efficient non-bonded van der Waal’s interaction contributing most energy to interact with the Lupenone. Therefore, Lupenone interacted strongly at the active site conforming into higher structural stability throughout the dynamic evolution of the complex. Thus, this study perhaps comprehend the efficiency of Lupenone as lead molecule against SFV E1 spike protein for future therapeutic purpose.

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Pandya, Medha D., Shweta D. Dabhi, Prafulla K. Jha, and Rakesh Rawal. "Targeting MLL-CXXC Domain with Synthetic CpG Dinucleotides: Docking and Molecular Dynamics Simulation Based Approach." Advanced Materials Research 1141 (August 2016): 115–20. http://dx.doi.org/10.4028/www.scientific.net/amr.1141.115.

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Mixed lineage leukemia (MLL) is an aggressive type of childhood leukemia characterized by the presence of MLL fusion proteins resultant of chromosomal translocations affecting the MLL gene. These resulting chimeric proteins act as transcriptional regulators that take control of MLL targets. MLL fuses with more than 60 different partner genes, these fusion proteins retain the CXXC domain which binds to nonmethylated CpG DNA. The Molecular docking of CXXC domain and CpG dinucleotides were performed, large scale and long time (10 ns each) molecular dynamics simulation on CXXC domain wild type and AF9-MLL Fusion Protein have been performed to study the mechanism at atomic level. The effects of point mutation on DNA bindings were also studied through Molecular Docking. The results confirm that this point mutation have efficacy of interrupt the DNA bindings. Moreover, in-silico studies suggest external synthetic CpG DNA efficiently binds to CXXC domain and may be potential lead molecule for further in-vitro studies.

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Vedhashree, Jangampally, Raynee Kirthi, Abbaraju krishna sailaja, M. Suma kanth, Mallepally Deepa Reddy, and M. Praveen Kumar. "Ayurvedic Formulations for the Treatment of Covid -19." Biomedical Research and Clinical Reviews 6, no. 4 (March 24, 2022): 01–09. http://dx.doi.org/10.31579/2692-9406/108.

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Background and objective: To recognize natural phytochemicals from medicinal plants, in order to reutilize them against COVID-19 by the virtue of molecular dynamics (MD) simulation study and molecular docking study COVID-19 is a transmissible disease that is initiated and propagated through a new virus strain SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2). Since 31st December 2019 in Wuhan city of China and the infection has outspread globally infecting many countries. Methods: Molecular dynamics MD simulation interaction analysis, Salt bridge analysis, Flexibility analysis, Ace-2- rbd complex electrostatic component of binding energy calculation method. Results: Molecular docking studies has shown to be having two inhibitors against SARS-CoV-2 Mpro (Main protease), from Withania somnifera (Ashwagandha) (Withanoside V [10.32 kcal/mol] and Somniferine [9.62 kcal/mol]). Inconsolably, SARS-CoV-2 infection in patients with pre-existing disease conditions (e.g., hypertension and diabetes) can cause severe complications and, as a result, mortality. Conclusion: Hence from the present study it could be suggested that, the active phytochemicals from medicinal plants could potentially inhibit Mpro of SARS-CoV-2 and further equip the management strategy against COVID-19-a global contagion. Active phytoconstituents of Ayurvedic medicinal plants Withania somnifera (Ashwagandha) predicted to significantly hinder main protease (Mpro or 3Clpro) of SARS-CoV-2.Through molecular docking and molecular dynamic simulation study, Withanoside V, Somniferine were observed to impede the activity of SARS-CoV-2 Mpro.

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Adedeji, Eunice O., Gbolahan O. Oduselu, Olubanke O. Ogunlana, Segun Fatumo, Rainer Koenig, and Ezekiel Adebiyi. "Anopheles gambiae Trehalase Inhibitors for Malaria Vector Control: A Molecular Docking and Molecular Dynamics Study." Insects 13, no. 11 (November 19, 2022): 1070. http://dx.doi.org/10.3390/insects13111070.

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Trehalase inhibitors are considered safe alternatives for insecticides and fungicides. However, there are no studies testing these compounds on Anopheles gambiae, a major vector of human malaria. This study predicted the three-dimensional structure of Anopheles gambiae trehalase (AgTre) and identified potential inhibitors using molecular docking and molecular dynamics methods. Robetta server, C-I-TASSER, and I-TASSER were used to predict the protein structure, while the structural assessment was carried out using SWISS-MODEL, ERRAT, and VERIFY3D. Molecular docking and screening of 3022 compounds was carried out using AutoDock Vina in PyRx, and MD simulation was carried out using NAMD. The Robetta model outperformed all other models and was used for docking and simulation studies. After a post-screening analysis and ADMET studies, uniflorine, 67837201, 10406567, and Compound 2 were considered the best hits with binding energies of −6.9, −8.9, −9, and −8.4 kcal/mol, respectively, better than validamycin A standard (−5.4 kcal/mol). These four compounds were predicted to have no eco-toxicity, Brenk, or PAINS alerts. Similarly, they were predicted to be non-mutagenic, carcinogenic, or hepatoxic. 67837201, 10406567, and Compound 2 showed excellent stability during simulation. The study highlights uniflorine, 67837201, 10406567, and Compound 2 as good inhibitors of AgTre and possible compounds for malaria vector control.

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Mukherjee, Sunny, Sucharita Das, Navneeth Sriram, Sandipan Chakraborty, and Mahesh Kumar Sah. "In silico investigation of the role of vitamins in cancer therapy through inhibition of MCM7 oncoprotein." RSC Advances 12, no. 48 (2022): 31004–15. http://dx.doi.org/10.1039/d2ra03703c.

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Huang, Yechuan, Xicai Zhang, and Huayi Suo. "Interaction between β-lactoglobulin and EGCG under high-pressure by molecular dynamics simulation." PLOS ONE 16, no. 12 (December 21, 2021): e0255866. http://dx.doi.org/10.1371/journal.pone.0255866.

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The binding between β-lactoglobulin and epigallocatechin gallate (EGCG) under the pressure of 600 MPa was explored using molecular docking and molecular dynamics (MD) simulation. EGCG bound mainly in two regions with site 1 in internal cavity of the β-barrel and site 2 on the surface of protein. 150 ns MD was performed starting from the structure with the optimal binding energy at the two sites in molecular docking, respectively. It was found that the protein fluctuated greatly when small molecule bound to site 2 at 0.1 MPa, and the protein fluctuation and solvent accessible surface area became smaller under high-pressure. The binding of small molecules made the protein structure more stable with increasing of α-helix and β-sheet, while high-pressure destroyed α-helix of protein. The binding energy of small molecules at site 1was stronger than that at site 2 under 0.1 MPa, with stronger van der Waals and hydrophobic interaction at site 1 while more hydrogen bonds were present at site 2. The binding energy of both sites weakened under high-pressure, especially at site 1, causing the binding force to be weaker at site 1 than that at site 2 under high-pressure.

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Yuan, Jiaying, Yiqing Zhu, Jiayi Zhao, Li Li, Chengjie Zhu, Mingxia Chen, Yi Zhang, and Yan Shang. "Network Pharmacology, Molecular Docking and Molecular Dynamics Simulation Studies of the Molecular Targets and Mechanisms of ChuanKeZhi in the Treatment of COVID-19." Natural Product Communications 17, no. 8 (August 2022): 1934578X2211169. http://dx.doi.org/10.1177/1934578x221116977.

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Objectives: Coronavirus disease 2019 (COVID-19) has had a global impact and is spreading quickly. ChuanKeZhi injection (CKZI) is widely used in asthma patients. In this paper, we aimed to explore active compounds of CKZ and determine potential mechanisms against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through network pharmacology, molecular docking and dynamic simulation studies. Materials and Methods: We used the Systematic Pharmacology Database and Analysis Platform of Traditional Chinese Medicine (TCMSP) to screen active compounds and potential target proteins of CKZ. COVID-19 target genes were screened via the American National Center for Biotechnology Information (NCBI) gene database and human gene database (GeenCards). The protein interaction network was constructed by the Protein Interaction Network Database (Search Tool for the Retrieval of Interacting Genes/Proteins (STRING)) platform. GO enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed by the Metascape database. The main active compounds of CKZ were docked with angiotensin-converting enzyme 2 (ACE2), spike protein S1, and SARS-CoV-2-3CL pro and also docked with hub targets. We performed molecular dynamics (MD) simulation studies for validation. Results: We finally obtained 207 CKZ potential targets and 4681 potential COVID-19 targets. Key targets included mainly AKT1, TNF, IL6, VEGFA, IL1B, TP53, JUN, CASP3, etc. There were 217 Gene Ontology (GO) items in the GO enrichment analysis ( p < 0.05). The main KEGG pathways included the advanced glycation end products (AGE)- receptor for AGE (RAGE) signalling pathway in diabetic complications, rheumatoid arthritis, chemical carcinogenesis-receptor activation, alcoholic liver disease, etc. Molecular docking and dynamics simulation studies both exhibited great binding capacity. Conclusions: Network pharmacology, molecular docking and dynamics simulation studies were used to identify the potential and key targets, pharmacological functions, and therapeutic mechanisms of CKZI in the treatment of COVID-19. CKZI may be an effective and safe drug in COVID-19 treatment. However, further work is needed for validation.

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Evren, Asaf Evrim, Demokrat Nuha, and Leyla Yurttaş. "Focusing on the moderately active compound (MAC) in the design and development of strategies to optimize the apoptotic effect by molecular mechanics techniques." European Journal of Life Sciences 1, no. 3 (February 28, 2023): 118–26. http://dx.doi.org/10.55971/ejls.1209591.

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Today, chemotherapeutic agents are mostly used to fight cancer in clinics. But even though they have selectivity for cancer cells, their mechanism of action could result in necrosis. Therefore, we aimed to suggest new design strategies using a moderately active compound (MAC) to get better activity and increase the apoptotic effect in this study. Although MAC, previously synthesized and evaluated for its anticancer properties, has been marked as a moderately active compound, it has let us develop new molecules using its molecular core supported by molecular docking and molecular dynamics simulation. The caspase-3 enzyme was subjected to density functional theory (DFT), docking, and molecular dynamics simulation studies, and the results were analyzed to better understand the structure-activity relationship (SAR); thus, new design strategies were proposed.

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Salehi, Farnaz, Leila Emami, Zahra Rezaei, Soghra Khabnadideh, Behnaz Tajik, and Razieh Sabet. "Fluconazole-Like Compounds as Potential Antifungal Agents: QSAR, Molecular Docking, and Molecular Dynamics Simulation." Journal of Chemistry 2022 (March 31, 2022): 1–16. http://dx.doi.org/10.1155/2022/5031577.

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Today, fungal infection has become more common disease especially in some cases, such as AIDS, cancer, and organ transplant which the immune system is suppressed. On the other hand, due to the increasing resistance to current antifungal drugs, more and more options for design of novel more efficient compounds with higher resistance are needed. In this study, a series of a fluconazole analogues were subjected to quantitative structure-activity relationship analysis to find the structure requirements for modeling adequate candidate. The best multiple linear regression equation was achieved from GA-PLS and MLR modeling. Subsequently, in silico screening study was applied to found new potent lead compounds based on the resulted model. The ability of the best designed compounds for antifungal activity was investigated by using molecular dynamic (MD) and molecular docking simulation. The results showed that compound F13 can efficiently bind to lanestrol 14-α demethylase target similar to other antifungal azoles. The molecular docking studies revealed an interesting binding profile with very high receptor affinity to the CYP51 active site. The triazole moiety of ligand F13 pointed to HEM group in lanestrol 14-α demethylase site and coordinated to Fe of HEM through its N4 atom. Also, there was a convenient relevance between QSAR and docking results. With the compound F13 which demonstrated the most promising minimum inhibitory concentration (MIC) values, it can be concluded that F13 is appropriate candidate for the development as antifungal agent.

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Abdjan, Muhammad Ikhlas, Nanik Siti Aminah, Alfinda Novi Kristanti, Imam Siswanto, Baso Ilham, Andika Pramudya Wardana, and Yoshiaki Takaya. "Structure-based approach: molecular insight of pyranocumarins against α-glucosidase through computational studies." RSC Advances 13, no. 6 (2023): 3438–47. http://dx.doi.org/10.1039/d2ra07537g.

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We presented the structure-based approach (molecular docking and MD simulation) to understand the dynamics behavior and inhibitory efficiency of pyranocoumarin derivatives against α-glucosidase at the molecular level.

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Khade, Amol B., Sidhartha S. Kar, Cinu T. Alummoottil, Ashutosh Tiwari, Mradul Tiwari, Vandana K. Eshwara, Pritesh Bhat, Varadaraj B. Giliyar, and Gurupur G. Shenoy. "Synthesis, Biological Evaluation and Molecular Dynamics Simulation Studies of Novel Diphenyl Ethers." Medicinal Chemistry 16, no. 2 (February 20, 2020): 256–70. http://dx.doi.org/10.2174/1573406415666190306152907.

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Background: The well-known antibacterial agent Triclosan (TCL) that targets bacterial enoylacyl protein reductase has been described to inhibit human fatty acid synthase (FASN) via the enoylacyl reductase domain. A Literature survey indicates that TCL is selectively toxic to cancer cells and furthermore might indeed reduce cancer incidence in vivo. A recent study found that TCL inhibits FASN by acting as an allosteric protein-protein interface (PPI) inhibitor. It induces dimer orientation changes that effect in a downstream reorientation of catalytic residues in the NADPH binding site proposing TCL as a viable scaffold to design a superior molecule that might have more inhibitory potential. This unveils tons of potential interaction space to take advantage of future inhibitor design. Objective: Synthesis of TCL mimicking novel diphenyl ether derivatives, biological evaluation as potential antiproliferative agents and molecular docking and molecular dynamics simulation studies. Methods: A series of novel N-(1-(3-hydroxy-4-phenoxyphenyl)-3-oxo-3-phenylpropyl)acetamides (3a-n) and N-(3(3-hydroxy-4phenoxyphenyl)-3-oxo-1-phenylpropyl) acetamides (6a-n) were designed, synthesized, characterized and evaluated against HepG2, A-549, MCF-7 and Vero cell lines. The induction of antiproliferative activity of selected compounds (3d and 6c) was done by AO/EB (acridine orange/ethidium bromide) nuclear staining method, DNA fragmentation study, and cell cycle analysis was performed by flow cytometry. Molecular docking and dynamics simulation study was also performed. Results: Among the tested compounds, compound 3d was most active (IC50 13.76 ± 0.43 µM) against A-549 cell line. Compounds 3d and 3g were found to be moderately active with IC50 30.56 ± 1.1 µM and 25.05 ± 0.8 µM respectively against MCF-7 cell line. Morphological analysis of A-549 cells treated with 3d and 6c clearly demonstrated the reduction of cell viability and induction of apoptosis. DNA fragmentation was observed as a characteristic of apoptosis in treated cells. Further, cell cycle analysis by flow cytometry confirmed that compounds 3d and 6c significantly arrested the cell cycle at the G0/G1 phase. Molecular docking study demonstrated that these compounds exhibit high affinity for the human fatty acid synthase (hFASN) target. Molecular dynamics simulation study of the most active compound 3d was performed for calculating binding free energies using Molecular Mechanics–Generalized Born Surface Area (MM/GBSA). Conclusion: Compound 3d (IC50 13.76 ± 0.43 µM) has been identified as a potential lead molecule for anticancer activity against A-549 cells followed by 3l, 6c, and 3g. Thus, the design of diphenyl ether derivatives with enhanced affinity to the binding site of hER may lead to the discovery of potential anticancer agents.

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Tripathi, Manish Kumar, Mohammad Yasir, Pushpendra Singh, and Rahul Shrivastava. "A Comparative Study to Explore the Effect of Different Compounds in Immune Proteins of Human Beings Against Tuberculosis: An In-silico Approach." Current Bioinformatics 15, no. 2 (March 10, 2020): 155–64. http://dx.doi.org/10.2174/1574893614666190226153553.

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Background: The lungs are directly exposed to pollutants, pathogens, allergens, and chemicals, which might lead to physiological disorders. During the Bhopal gas disaster, the lungs of the victims were exposed to various chemicals. Here, using molecular modelling studies, we describe the effects of these chemicals (Dimethyl urea, Trimethyl urea, Trimethyl isocyanurate, Alphanaphthol, Butylated hydroxytoluene and Carbaryl) on pulmonary immune proteins. Objective: In the current study, we performed molecular modelling methods like molecular docking and molecular dynamics simulation studies to identify the effects of hydrolytic products of MIC and dumped residues on the pulmonary immune proteins. Methods: Molecular docking studies of (Dimethyl urea, Trimethyl urea, Trimethyl isocyanurate, Alphanaphthol, Butylated hydroxytoluene and Carbaryl) on pulmonary immune proteins was performed using the Autodock 4.0 tool, and gromacs was used for the molecular dynamics simulation studies to get an insight into the possible mode of protein-ligand interactions. Further, in silico ADMET studies was performed using the TOPKAT protocol of discovery studio. Results: From docking studies, we found that surfactant protein-D is inhibited most by the chemicals alphanaphthol (dock score, -5.41Kcal/mole), butylated hydroxytoluene (dock score,-6.86 Kcal/mole), and carbaryl (dock score,-6.1 Kcal/mole). To test their stability, the obtained dock poses were placed in a lipid bilayer model system mimicking the pulmonary surface. Molecular dynamics simulations suggest a stable interaction between surfactant protein-D and carbaryl. Conclusion: This, study concludes that functioning of surfactant protein-D is directly or indirectly affected by the carbaryl chemical, which might account for the increased susceptibility of Bhopal gas disaster survivors to pulmonary tuberculosis.

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Rizqillah, Raihan Kenji, Jaka Fajar Fatriansyah, Fadilah, Sulhadi, Siti Wahyuni, Muhammad Arif Sudirman, Helya Chafshoh Nafisah, and Sukma Dewi Lestari. "In silico molecular docking and molecular dynamics examination of Andrographis paniculata compounds of Andrographolide, Neoandrographolide, and 5-hydroxy-7,8,2’,3’-tetramethoxyflavone inhibition activity to SARS-CoV-2 main protease." BIO Web of Conferences 41 (2021): 07002. http://dx.doi.org/10.1051/bioconf/20214107002.

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In this work, Andrographis paniculata compounds of Andrographolide, Neoandrographolide, and 5-hydroxy-7,8,2’,3’-tetramethoxyflavone inhibition activity to SARS CoV-2 main protease were examined through in silico molecular docking and molecular dynamics simulation, with Remdesivir as control ligand. Docking score and MMGBSA were examined as well as molecular dynamics parameters: RMSD, RMSF and Protein ligand contact fraction. Our study found that Andrographis paniculata compounds of Andrographolide, Neoandrographolide, and 5-hydroxy-7,8,2’,3’-tetramethoxyflavone have comparable inhibition activity to SARS CoV-2 main protease in comparison to Remdesivir. 5-hydroxy7,8,2’,3’-tetramethoxyflavone has the lowest docking score, which was further validated by protein ligand contact fraction examination, although MMGBSA score is lowest for Remdesivir.

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Halder, Sajal Kumar, Maria Mulla Mim, Md Meharab Hassan Alif, Jannatul Fardous Shathi, Nuhu Alam, Aparna Shil, and Mahbubul Kabir Himel. "Oxa-376 and Oxa-530 variants of β-lactamase: computational study uncovers potential therapeutic targets of Acinetobacter baumannii." RSC Advances 12, no. 37 (2022): 24319–38. http://dx.doi.org/10.1039/d2ra02939a.

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Determining novel therapeutic targets of Acinetobacter baumannii. Deleterious variants, causing antibiotic resistance, were identified by molecular docking and molecular dynamics simulation suggesting new therapeutic targets Oxa-376 and Oxa-530.

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Kalva, Sukesh, Nikhil Agrawal, Adam A. Skelton, and Lilly M. Saleena. "Identification of novel selective MMP-9 inhibitors as potential anti-metastatic lead using structure-based hierarchical virtual screening and molecular dynamics simulation." Molecular BioSystems 12, no. 8 (2016): 2519–31. http://dx.doi.org/10.1039/c6mb00066e.

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Abdjan, Muhammad Ikhlas, Nanik Siti Aminah, Imam Siswanto, Alfinda Novi Kristanti, Yoshiaki Takaya, and Muhammad Iqbal Choudhary. "Exploration of stilbenoid trimers as potential inhibitors of sirtuin1 enzyme using a molecular docking and molecular dynamics simulation approach." RSC Advances 11, no. 31 (2021): 19323–32. http://dx.doi.org/10.1039/d1ra02233d.

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Shi, Mingsong, Min Zhao, Lun Wang, Kongjun Liu, Penghui Li, Jiang Liu, Xiaoying Cai, Lijuan Chen, and Dingguo Xu. "Exploring the stability of inhibitor binding to SIK2 using molecular dynamics simulation and binding free energy calculation." Physical Chemistry Chemical Physics 23, no. 23 (2021): 13216–27. http://dx.doi.org/10.1039/d1cp00717c.

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The detailed interactions between SIK2 and four inhibitors, HG-9-91-01, KIN112, MRT67307, and MRT199665, were studied using molecular docking, molecular dynamics simulation, binding free energy calculation, and interaction fingerprint analysis.

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Sama-ae, Imran, Suthinee Sangkanu, Abolghasem Siyadatpanah, Roghayeh Norouzi, Julalak Chuprom, Watcharapong Mitsuwan, Sirirat Surinkaew, et al. "Targeting Acanthamoeba proteins interaction with flavonoids of Propolis extract by in vitro and in silico studies for promising therapeutic effects." F1000Research 11 (February 7, 2023): 1274. http://dx.doi.org/10.12688/f1000research.126227.2.

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Background: Propolis is a natural resinous mixture produced by bees. It provides beneficial effects on human health in the treatment/management of many diseases. The present study was performed to demonstrate the anti-Acanthamoeba activity of ethanolic extracts of Propolis samples from Iran. The interactions of the compounds and essential proteins of Acanthamoeba were also visualized through docking simulation. Methods: The minimal inhibitory concentrations (MICs) of Propolis extract against Acanthamoeba trophozoites and cysts was determined in vitro. In addition, two-fold dilutions of each of the agents were tested for encystment, excystment and adhesion inhibitions. Three major compounds of Propolis extract such as chrysin, tectochrysin and pinocembrin have been selected in molecular docking approach to predict the compounds that might be responsible for encystment, excystment and adhesion inhibitions of A. castellanii. Furthermore, to confirm the docking results, molecular dynamics (MD) simulations were also carried out for the most promising two ligand-pocket complexes from docking studies. Results: The minimal inhibitory concentrations (MICs) 62.5 and 125 µg/mL of the most active Propolis extract were assessed in trophozoites stage of Acanthamoeba castellanii ATCC30010 and ATCC50739, respectively. At concentrations lower than their MICs values (1/16 MIC), Propolis extract revealed inhibition of encystation. However, at 1/2 MIC, it showed a potential inhibition of excystation and anti-adhesion. The molecular docking and dynamic simulation revealed the potential capability of Pinocembrin to form hydrogen bonds with A. castellanii Sir2 family protein (AcSir2), an encystation protein of high relevance for this process in Acanthamoeba. Conclusions: The results obtained provided a candidate for the development of therapeutic drugs against Acanthamoeba infection. In vivo experiments and clinical trials are necessary to support this claim.

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Sama-ae, Imran, Suthinee Sangkanu, Abolghasem Siyadatpanah, Roghayeh Norouzi, Julalak Chuprom, Watcharapong Mitsuwan, Sirirat Surinkaew, et al. "Targeting Acanthamoeba proteins interaction with flavonoids of Propolis extract by in vitro and in silico studies for promising therapeutic effects." F1000Research 11 (November 8, 2022): 1274. http://dx.doi.org/10.12688/f1000research.126227.1.

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Background: Propolis is a natural resinous mixture produced by bees. It provides beneficial effects on human health in the treatment/management of many diseases. The present study was performed to demonstrate the anti-Acanthamoeba activity of ethanolic extracts of Propolis samples from Iran. The interactions of the compounds and essential proteins of Acanthamoeba were also visualized through docking simulation. Methods: The minimal inhibitory concentrations (MICs) of Propolis extract against Acanthamoeba trophozoites and cysts was determined in vitro. In addition, two-fold dilutions of each of the agents were tested for encystment, excystment and adhesion inhibitions. Three major compounds of Propolis extract such as chrysin, tectochrysin and pinocembrin have been selected in molecular docking approach to predict the compounds that might be responsible for encystment, excystment and adhesion inhibitions of A. castellanii. Furthermore, to confirm the docking results, molecular dynamics (MD) simulations were also carried out for the most promising two ligand-pocket complexes from docking studies. Results: The minimal inhibitory concentrations (MICs) 62.5 and 125 µg/mL of the most active Propolis extract were assessed in trophozoites stage of Acanthamoeba castellanii ATCC30010 and ATCC50739, respectively. At concentrations lower than their MICs values (1/16 MIC), Propolis extract revealed inhibition of encystation. However, at 1/2 MIC, it showed a potential inhibition of excystation and anti-adhesion. The molecular docking and dynamic simulation revealed the potential capability of Pinocembrin to form hydrogen bonds with A. castellanii Sir2 family protein (AcSir2), an encystation protein of high relevance for this process in Acanthamoeba. Conclusions: The results obtained provided a candidate for the development of therapeutic drugs against Acanthamoeba infection. In vivo experiments and clinical trials are necessary to support this claim.

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Xiong, Weixue, Jiahui Cai, Ruijia Li, Canhong Wen, and Haizhu Tan. "Rare Variant Analysis and Molecular Dynamics Simulation in Alzheimer’s Disease Identifies Exonic Variants in FLG." Genes 13, no. 5 (May 7, 2022): 838. http://dx.doi.org/10.3390/genes13050838.

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Background: Although an increasing number of common variants contributing to Alzheimer’s disease (AD) are uncovered by genome-wide association studies, they can only explain less than half of the heritability of AD. Rare variant association studies (RVAS) has become an increasingly important area to explain the risk or trait variability of AD. Method: To investigate the potential rare variants that cause AD, we screened 70,209 rare variants from two cohorts of a 175 AD cohort and a 214 cognitively normal cohort from the Alzheimer’s Disease Neuroimaging Initiative database. MIRARE, a novel RVAS method, was performed on 232 non-synonymous variants selected by ANNOVAR annotation. Molecular docking and molecular dynamics (MD) simulation were adopted to verify the interaction between the chosen functional variants and BACE1. Results: MIRAGE analysis revealed significant associations between AD and six potential pathogenic genes, including PREX2, FLG, DHX16, NID2, ZnF585B and ZnF875. Only interactions between FLG (including wild type and rs3120654(SER742TYR)) and BACE1 were verified by molecular docking and MD simulation. The interaction of FLG(SER742TYR) with BACE1 was greater than that of wildtype FLG with BACE1. Conclusions: According to the literature search, bio-informatics analysis, and molecular docking and MD simulation, we find non-synonymous rare variants in six genes, especially FLG(rs3120654), that may play key roles in AD.

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Gervasoni, Silvia, Carmine Talarico, Candida Manelfi, Alessandro Pedretti, Giulio Vistoli, and Andrea R. Beccari. "Extensive Sampling of Molecular Dynamics Simulations to Identify Reliable Protein Structures for Optimized Virtual Screening Studies: The Case of the hTRPM8 Channel." International Journal of Molecular Sciences 23, no. 14 (July 8, 2022): 7558. http://dx.doi.org/10.3390/ijms23147558.

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(1) Background: Virtual screening campaigns require target structures in which the pockets are properly arranged for binding. Without these, MD simulations can be used to relax the available target structures, optimizing the fine architecture of their binding sites. Among the generated frames, the best structures can be selected based on available experimental data. Without experimental templates, the MD trajectories can be filtered by energy-based criteria or sampled by systematic analyses. (2) Methods: A blind and methodical analysis was performed on the already reported MD run of the hTRPM8 tetrameric structures; a total of 50 frames underwent docking simulations by using a set of 1000 ligands including 20 known hTRPM8 modulators. Docking runs were performed by LiGen program and involved the frames as they are and after optimization by SCRWL4.0. For each frame, all four monomers were considered. Predictive models were developed by the EFO algorithm based on the sole primary LiGen scores. (3) Results: On average, the MD simulation progressively enhances the performance of the extracted frames, and the optimized structures perform better than the non-optimized frames (EF1% mean: 21.38 vs. 23.29). There is an overall correlation between performances and volumes of the explored pockets and the combination of the best performing frames allows to develop highly performing consensus models (EF1% = 49.83). (4) Conclusions: The systematic sampling of the entire MD run provides performances roughly comparable with those previously reached by using rationally selected frames. The proposed strategy appears to be helpful when the lack of experimental data does not allow an easy selection of the optimal structures for docking simulations. Overall, the reported docking results confirm the relevance of simulating all the monomers of an oligomer structure and emphasize the efficacy of the SCRWL4.0 method to optimize the protein structures for docking calculations.

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Journal articles on the topic 'Molecuar dynamics and docking simulation'

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