Molecular modelling on SARS-CoV-2 papain-like protease: an integrated study with homology modelling, molecular docking, and molecular dynamics simulations

2021 ◽  
pp. 1-20
Author(s):  
A. Arwansyah ◽  
A.R. Arif ◽  
I. Ramli ◽  
I. Kurniawan ◽  
S. Sukarti ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulations ◽  
Molecular Modelling ◽  
Homology Modelling ◽  
Dynamics Simulations ◽  
Integrated Study

scholarly journals Molecular modelling studies of quinazolinone derivatives as MMP-13 inhibitors by QSAR, molecular docking and molecular dynamics simulations techniques

MedChemComm ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 101-115 ◽  
Author(s):  
Shanshan Huang ◽  
Kairui Feng ◽  
Yujie Ren
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulations ◽  
Molecular Modelling ◽  
Molecular Modelling Studies ◽  
Qsar Models ◽  
Modelling Studies ◽  
Dynamics Simulations ◽  
Quinazolinone Derivatives

Reliable QSAR models for quinazolinones were constructed and eight novel MMP-13 inhibitors with higher predictive activity were identified.

scholarly journals Virtual Repurposing of Ursodeoxycholate and Chenodeoxycholate as Lead Candidates Against SARS-Cov2-Envelope Protein: A Molecular Dynamics Investigation

2020 ◽  
Author(s):  
Reena Yadav ◽  
chinmayee choudhury ◽  
Yashwant Kumar ◽  
Alka Bhatia
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulations ◽  
Envelope Protein ◽  
Homology Modelling ◽  
Protein A ◽  
Drug Repurposing ◽  
Dynamics Simulations ◽  
Global Threat ◽  
Polar Functional Groups

Drug repurposing is an apt choice to combat the currently prevailing global threat of COVID-19, caused by SARS-Cov2 in absence of any specific medication/vaccine. The present work attempts to computationally evaluate binding affinities and effect of two widely used surfactant drugs i.e. chenodeoxycholate (CDC) and ursodeoxycholate (UDC) with the envelope protein of SARS-Cov2 (SARS-Cov2-E) using homology modelling, molecular docking and molecular dynamics simulations. A good quality homo-pentameric structure of SARS-Cov2-E was modelled from its homologue with more than 90% sequence identity followed by symmetric docking. The pentameric structure was embedded in a DPPC membrane and subsequently energy minimized. The minimized structure was used for blind molecular docking of CDC and UDC to obtain the best scoring SARS-Cov2-E–CDC/UDC complexes, which were subjected to 230ns molecular dynamics simulations in triplicates in DPPC membrane environment. Comparative analyses of structural and enthalpic properties and molecular interaction profiles from the MD trajectories revealed that, both CDC and UDC could stably bind to SARS-Cov2-E through H-bonds, water-bridges and hydrophobic contacts in the transmembraneresidues.T30 was observed to be a key residue for CDC/UDC binding. The polar functional groups of the bound CDC/UDC facilitated entry of a large number of water molecules into the channel and affected the H-bonding pattern between adjacent monomeric chains, loosening the compact transmembrane region of SARS-Cov2-E. These observations suggest the potential of CDC/UDC as repurposed candidates to hinder the survival of SARS-Cov2 by disrupting the structure of SARS-Cov2-E and facilitate entry of solvents/polar inhibitors inside the viral cell.

scholarly journals Virtual Repurposing of Ursodeoxycholate and Chenodeoxycholate as Lead Candidates Against SARS-Cov2-Envelope Protein: A Molecular Dynamics Investigation

2020 ◽  
Author(s):  
Reena Yadav ◽  
chinmayee choudhury ◽  
Yashwant Kumar ◽  
Alka Bhatia
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulations ◽  
Envelope Protein ◽  
Homology Modelling ◽  
Protein A ◽  
Drug Repurposing ◽  
Dynamics Simulations ◽  
Global Threat ◽  
Polar Functional Groups

Drug repurposing is an apt choice to combat the currently prevailing global threat of COVID-19, caused by SARS-Cov2 in absence of any specific medication/vaccine. The present work attempts to computationally evaluate binding affinities and effect of two widely used surfactant drugs i.e. chenodeoxycholate (CDC) and ursodeoxycholate (UDC) with the envelope protein of SARS-Cov2 (SARS-Cov2-E) using homology modelling, molecular docking and molecular dynamics simulations. A good quality homo-pentameric structure of SARS-Cov2-E was modelled from its homologue with more than 90% sequence identity followed by symmetric docking. The pentameric structure was embedded in a DPPC membrane and subsequently energy minimized. The minimized structure was used for blind molecular docking of CDC and UDC to obtain the best scoring SARS-Cov2-E–CDC/UDC complexes, which were subjected to 230ns molecular dynamics simulations in triplicates in DPPC membrane environment. Comparative analyses of structural and enthalpic properties and molecular interaction profiles from the MD trajectories revealed that, both CDC and UDC could stably bind to SARS-Cov2-E through H-bonds, water-bridges and hydrophobic contacts in the transmembraneresidues.T30 was observed to be a key residue for CDC/UDC binding. The polar functional groups of the bound CDC/UDC facilitated entry of a large number of water molecules into the channel and affected the H-bonding pattern between adjacent monomeric chains, loosening the compact transmembrane region of SARS-Cov2-E. These observations suggest the potential of CDC/UDC as repurposed candidates to hinder the survival of SARS-Cov2 by disrupting the structure of SARS-Cov2-E and facilitate entry of solvents/polar inhibitors inside the viral cell.

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