scholarly journals New Binding Site Conformations of the Dengue Virus NS3 Protease Accessed by Molecular Dynamics Simulation

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e72402 ◽  
Author(s):  
Hugo de Almeida ◽  
Izabela M. D. Bastos ◽  
Bergmann M. Ribeiro ◽  
Bernard Maigret ◽  
Jaime M. Santana
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Dengue Virus ◽  
Binding Site ◽  
Dynamics Simulation ◽  
Ns3 Protease

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.

scholarly journals Modification ofS-Adenosyl-l-Homocysteine as Inhibitor of Nonstructural Protein 5 Methyltransferase Dengue Virus Through Molecular Docking and Molecular Dynamics Simulation

2017 ◽  
Vol 11 ◽  
pp. 117739281770172 ◽  
Author(s):  
Usman Sumo Friend Tambunan ◽  
Mochammad Arfin Fardiansyah Nasution ◽  
Fauziah Azhima ◽  
Arli Aditya Parikesit ◽  
Erwin Prasetya Toepak ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulation ◽  
Dengue Virus ◽  
Nonstructural Protein ◽  
Dynamics Simulation
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