About: Elucidating biophysical basis of binding of inhibitors to SARS-CoV-2 main protease by using molecular dynamics simulations and free energy calculations

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About: Elucidating biophysical basis of binding of inhibitors to SARS-CoV-2 main protease by using molecular dynamics simulations and free energy calculations Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Elucidating biophysical basis of binding of inhibitors to SARS-CoV-2 main protease by using molecular dynamics simulations and free energy calculations
Creator	Kar, Parimal Jonniya, Nisha Poddar, Sayan Roy, Rajarshi Sk, Fulbabu
Source	Medline; PMC
abstract	The recent outbreak of novel “coronavirus disease 2019” (COVID-19) has spread rapidly worldwide, causing a global pandemic. In the present work, we have elucidated the mechanism of binding of two inhibitors, namely α-ketoamide and Z31792168, to SARS-CoV-2 main protease (M(pro) or 3CL(pro)) by using all-atom molecular dynamics simulations and free energy calculations. We calculated the total binding free energy (ΔG(bind)) of both inhibitors and further decomposed ΔG(bind) into various forces governing the complex formation using the Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) method. Our calculations reveal that α-ketoamide is more potent (ΔG(bind)= − 9.05 kcal/mol) compared to Z31792168 (ΔG(bind)= − 3.25 kcal/mol) against COVID-19 3CL(pro). The increase in ΔG(bind) for α-ketoamide relative to Z31792168 arises due to an increase in the favorable electrostatic and van der Waals interactions between the inhibitor and 3CL(pro). Further, we have identified important residues controlling the 3CL(pro)-ligand binding from per-residue based decomposition of the binding free energy. Finally, we have compared ΔG(bind) of these two inhibitors with the anti-HIV retroviral drugs, such as lopinavir and darunavir. It is observed that α-ketoamide is more potent compared to lopinavir and darunavir. In the case of lopinavir, a decrease in van der Waals interactions is responsible for the lower binding affinity compared to α-ketoamide. On the other hand, in the case of darunavir, a decrease in the favorable intermolecular electrostatic and van der Waals interactions contributes to lower affinity compared to α-ketoamide. Our study might help in designing rational anti-coronaviral drugs targeting the SARS-CoV-2 main protease. Communicated by Ramaswamy H. Sarma
has issue date	2020-06-01(xsd:dateTime)
bibo:doi	10.1080/07391102.2020.1768149
bibo:pmid	32396767
has license	no-cc
sha1sum (hex)	c409519ba2da8fecb7294f93ecf25d832eb9e144
schema:url	https://doi.org/10.1080/07391102.2020.1768149
resource representing a document's title	Elucidating biophysical basis of binding of inhibitors to SARS-CoV-2 main protease by using molecular dynamics simulations and free energy calculations
has PubMed Central identifier	PMC7284146
has PubMed identifier	32396767
schema:publication	J Biomol Struct Dyn
resource representing a document's body	covid:c409519ba2da8fecb7294f93ecf25d832eb9e144#body_text
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