Elucidating biophysical basis of binding of inhibitors to SARS-CoV-2 main protease by using molecular dynamics simulations and free energy calculations
Md Fulbabu Sk, Rajarshi Roy, Nisha Amarnath Jonniya, Sayan Poddar, Parimal Kar
Abstract
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.
Topics & Concepts
ProteaseMolecular dynamicsBasis (linear algebra)Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Dynamics (music)Computational biologyCoronavirus disease 2019 (COVID-19)Statistical physicsChemistryBiophysicsComputational chemistryBiologyPhysicsEnzymeMedicineBiochemistryMathematicsGeometryDiseasePathologyInfectious disease (medical specialty)AcousticsComputational Drug Discovery MethodsProtein Structure and DynamicsSARS-CoV-2 and COVID-19 Research