scholarly journals Identification of Potential Binders of the SARS-Cov-2 Spike Protein via Molecular Docking, Dynamics Simulation and Binding Free Energy Calculation

2020 ◽  
Author(s):  
Dr. Chirag N. Patel ◽  
Dr. Prasanth Kumar S. ◽  
Dr. Himanshu A. Pandya ◽  
Dr. Rakesh M. Rawal
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Molecular Docking ◽  
Molecular Dynamics Simulations ◽  
Binding Free Energy ◽  
Free Energy Calculations ◽  
Dynamics Simulation ◽  
Spike Protein ◽  
Energy Calculations ◽  
Dynamics Simulations

<p>The pandemic outbreak of COVID-19 virus (SARS-CoV-2) has become critical global health issue. The biophysical and structural evidence shows that SARS-CoV-2 spike protein possesses higher binding affinity towards angiotensin-converting enzyme 2 (ACE2) and hemagglutinin-acetylesterase (HE) glycoprotein receptor. Hence, it was selected as a target to generate the potential candidates for the inhibition of HE glycoprotein. The present study focuses on extensive computational approaches which contains molecular docking, ADMET prediction followed by molecular dynamics simulations and free energy calculations. Furthermore, virtual screening of NPACT compounds identified 3,4,5-Trihydroxy-1,8-bis[(2R,3R)-3,5,7-trihydroxy-3,4-dihydro-2H-chromen-2-yl]benzo[7]annulen-6-one, Silymarin, Withanolide D, Spirosolane and Oridonin were interact with high affinity. The ADMET prediction revealed pharmacokinetics and drug-likeness properties of top-ranked compounds. Molecular dynamics simulations and binding free energy calculations affirmed that these five NPACT compounds were robust HE inhibitor.</p>

scholarly journals Identification of Potential Binders of the SARS-Cov-2 Spike Protein via Molecular Docking, Dynamics Simulation and Binding Free Energy Calculation

2020 ◽  
Author(s):  
Dr. Chirag N. Patel ◽  
Dr. Prasanth Kumar S. ◽  
Dr. Himanshu A. Pandya ◽  
Dr. Rakesh M. Rawal
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Molecular Docking ◽  
Molecular Dynamics Simulations ◽  
Binding Free Energy ◽  
Free Energy Calculations ◽  
Dynamics Simulation ◽  
Spike Protein ◽  
Energy Calculations ◽  
Dynamics Simulations

<p>The pandemic outbreak of COVID-19 virus (SARS-CoV-2) has become critical global health issue. The biophysical and structural evidence shows that SARS-CoV-2 spike protein possesses higher binding affinity towards angiotensin-converting enzyme 2 (ACE2) and hemagglutinin-acetylesterase (HE) glycoprotein receptor. Hence, it was selected as a target to generate the potential candidates for the inhibition of HE glycoprotein. The present study focuses on extensive computational approaches which contains molecular docking, ADMET prediction followed by molecular dynamics simulations and free energy calculations. Furthermore, virtual screening of NPACT compounds identified 3,4,5-Trihydroxy-1,8-bis[(2R,3R)-3,5,7-trihydroxy-3,4-dihydro-2H-chromen-2-yl]benzo[7]annulen-6-one, Silymarin, Withanolide D, Spirosolane and Oridonin were interact with high affinity. The ADMET prediction revealed pharmacokinetics and drug-likeness properties of top-ranked compounds. Molecular dynamics simulations and binding free energy calculations affirmed that these five NPACT compounds were robust HE inhibitor.</p>

scholarly journals Elucidating Biophysical Basis of Binding of Inhibitors to SARS-CoV-2 Main Protease by Using Molecular Dynamics Simulations and Free Energy Calculations

2020 ◽  
Author(s):  
Md Fulbabu Sk ◽  
Rajarshi Roy ◽  
Nisha Amarnath Jonniya ◽  
Sayan Poddar ◽  
Parimal Kar
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Molecular Dynamics Simulations ◽  
Binding Free Energy ◽  
Van Der Waals ◽  
Antiviral Drug ◽  
Free Energy Calculations ◽  
Energy Calculations ◽  
Main Protease ◽  
Dynamics Simulations

<div>The recent outbreak of novel “coronavirus disease 2019” (COVID-19) has spread rapidly</div><div>worldwide, causing a global pandemic. In the absence of a vaccine or a suitable</div><div>chemotherapeutic intervention, it is an urgent need to develop a new antiviral drug to fight this</div><div>deadly respiratory disease. In the present work, we have elucidated the mechanism of binding</div><div>of two inhibitors, namely α-ketoamide and Z31792168 to SARS-CoV-2 main protease (Mpro</div><div>or 3CLpro) by using all-atom molecular dynamics simulations and free energy calculations. We</div><div>calculated the total binding free energy (ΔGbind) of both inhibitors and further decomposed</div><div>ΔGbind into various forces governing the complex formation using the Molecular</div><div>Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) method. Our calculations reveal</div><div>that α-ketoamide is more potent (ΔGbind= - 9.05 kcal/mol) compared to Z31792168 (ΔGbind= -</div><div>3.25 kcal/mol) against COVID-19 3CLpro. The increase in ΔGbind for α-ketoamide relative to</div><div>Z31792168 arises due to an increase in the favorable electrostatic and van der Waals</div><div>interactions between the inhibitor and 3CLpro. Further, we have identified important residues</div><div>controlling the 3CLpro-ligand binding from per-residue based decomposition of the binding free</div><div>energy. Finally, we have compared ΔGbind of these two inhibitors with the anti-HIV retroviral</div><div>drugs, such as lopinavir and darunavir. It is observed that α-ketoamide is more potent compared</div><div>to both lopinavir and darunavir. In the case of lopinavir, a decrease in the size of the van der</div><div>Waals interactions is responsible for the lower binding affinity compared to α-ketoamide. On</div><div>the other hand, in the case of darunavir, a decrease in the favorable intermolecular electrostatic</div><div>and van der Waals interactions contributes to lower affinity compared to α-ketoamide. Our</div><div>study might help in designing rational anticoronaviral drugs targeting the SARS-CoV-2 main</div><div>protease. </div>

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