The molecular mechanism of two coreceptor binding site antibodies X5 and 17b neutralizing HIV-1: Insights from molecular dynamics simulation

2018 ◽  
Vol 92 (1) ◽  
pp. 1357-1365 ◽  
Author(s):  
Yan Zhang ◽  
Jingjing Guo ◽  
Le Huang ◽  
Jiaqi Tian ◽  
Xiaojun Yao ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Binding Site ◽  
Molecular Mechanism ◽  
Dynamics Simulation ◽  
Coreceptor Binding ◽  
Hiv 1 ◽  
Coreceptor Binding Site

scholarly journals Prediction of Ciclesonide Binding Site on Middle-East Respiratory Syndrome Coronavirus Nsp15 Multimer by Molecular Dynamics Simulations

2021 ◽  
Author(s):  
Shun Sakuraba ◽  
Hidetoshi Kono
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Middle East ◽  
Molecular Dynamics Simulations ◽  
Binding Site ◽  
Molecular Mechanism ◽  
Middle East Respiratory Syndrome ◽  
Dynamics Simulation ◽  
Dynamics Simulations

Ciclesonide, a corticosteroid, was known to inhibit the growth of Middle-east respiratory syndrome (MERS) coronavirus. However, its molecular mechanism was unknown. We tried to uncover the molecular mechanism from the molecular dynamics simulation.<div>SARS_CoV_2_nsp15.pdf: The preprint document.</div><div>nsp15-mers-supp.zip: Supplemental data including binding poses and parameter files for the simulation.</div>

scholarly journals Prediction of Ciclesonide Binding Site on Middle-East Respiratory Syndrome Coronavirus Nsp15 Multimer by Molecular Dynamics Simulations

2021 ◽  
Author(s):  
Shun Sakuraba ◽  
Hidetoshi Kono
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Middle East ◽  
Molecular Dynamics Simulations ◽  
Binding Site ◽  
Molecular Mechanism ◽  
Middle East Respiratory Syndrome ◽  
Dynamics Simulation ◽  
Dynamics Simulations

Ciclesonide, a corticosteroid, was known to inhibit the growth of Middle-east respiratory syndrome (MERS) coronavirus. However, its molecular mechanism was unknown. We tried to uncover the molecular mechanism from the molecular dynamics simulation.<div>SARS_CoV_2_nsp15.pdf: The preprint document.</div><div>nsp15-mers-supp.zip: Supplemental data including binding poses and parameter files for the simulation.</div>

Unveiling the Structural Insights into the Selective Inhibition of Protein Kinase D1

2019 ◽  
Vol 25 (10) ◽  
pp. 1059-1074 ◽  
Author(s):  
Raju Dash ◽  
Md. Arifuzzaman ◽  
Sarmistha Mitra ◽  
Md. Abdul Hannan ◽  
Nurul Absar ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Protein Kinase ◽  
Binding Site ◽  
Free Energy Calculations ◽  
Dynamics Simulation ◽  
Selective Inhibitors ◽  
Conserved Residues ◽  
Protein Kinase D1 ◽  
Binding Mechanisms

Background: Although protein kinase D1 (PKD1) has been proved to be an efficient target for anticancer drug development, lack of structural details and substrate binding mechanisms are the main obstacles for the development of selective inhibitors with therapeutic benefits. Objective: The present study described the in silico dynamics behaviors of PKD1 in binding with selective and non-selective inhibitors and revealed the critical binding site residues for the selective kinase inhibition. Methods: Here, the three dimensional model of PKD1 was initially constructed by homology modeling along with binding site characterization to explore the non-conserved residues. Subsequently, two known inhibitors were docked to the catalytic site and the detailed ligand binding mechanisms and post binding dyanmics were investigated by molecular dynamics simulation and binding free energy calculations. Results: According to the binding site analysis, PKD1 serves several non-conserved residues in the G-loop, hinge and catalytic subunits. Among them, the residues including Leu662, His663, and Asp665 from hinge region made polar interactions with selective PKD1 inhibitor in docking simulation, which were further validated by the molecular dynamics simulation. Both inhibitors strongly influenced the structural dynamics of PKD1 and their computed binding free energies were in accordance with experimental bioactivity data. Conclusion: The identified non-conserved residues likely to play critical role on molecular reorganization and inhibitor selectivity. Taken together, this study explained the molecular basis of PKD1 specific inhibition, which may help to design new selective inhibitors for better therapies to overcome cancer and PKD1 dysregulated disorders.

scholarly journals A molecular dynamics simulation study of the ACE2 receptor with screened natural inhibitors to identify novel drug candidate against COVID-19

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11171
Author(s):  
Neha Srivastava ◽  
Prekshi Garg ◽  
Prachi Srivastava ◽  
Prahlad Kishore Seth
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulation ◽  
Binding Site ◽  
Cinnamic Acid ◽  
Simulation Study ◽  
Computational Study ◽  
Dynamics Simulation ◽  
Receptor Protein ◽  
Novel Therapeutic

Background & Objectives The massive outbreak of Novel Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) has turned out to be a serious global health issue worldwide. Currently, no drugs or vaccines are available for the treatment of COVID-19. The current computational study was attempted to identify a novel therapeutic inhibitor against novel SARS-CoV-2 using in silico drug discovery pipeline. Methods In the present study, the human angiotensin-converting enzyme 2 (ACE2) receptor was the target for the designing of drugs against the deadly virus. The 3D structure of the receptor was modeled & validated using a Swiss-model, Procheck & Errat server. A molecular docking study was performed between a group of natural & synthetic compounds having proven anti-viral activity with ACE2 receptor using Autodock tool 1.5.6. The molecular dynamics simulation study was performed using Desmond v 12 to evaluate the stability and interaction of the ACE2 receptor with a ligand. Results Based on the lowest binding energy, confirmation, and H-bond interaction, cinnamic acid (−5.20 kcal/mol), thymoquinone (−4.71 kcal/mol), and andrographolide (Kalmegh) (−4.00 kcal/mol) were screened out showing strong binding affinity to the active site of ACE2 receptor. MD simulations suggest that cinnamic acid, thymoquinone, and andrographolide (Kalmegh) could efficiently activate the biological pathway without changing the conformation in the binding site of the ACE2 receptor. The bioactivity and drug-likeness properties of compounds show their better pharmacological property and safer to use. Interpretation & Conclusions The study concludes the high potential of cinnamic acid, thymoquinone, and andrographolide against the SARS-CoV-2 ACE2 receptor protein. Thus, the molecular docking and MD simulation study will aid in understanding the molecular interaction between ligand and receptor binding site, thereby leading to novel therapeutic intervention.

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