Exploring the effect of temperature on inhibition of non-structural protease 3 of Chikungunya virus using molecular dynamics simulations and thermodynamics parameters

摘要

Chikungunya viral infections are creating problems in humans, therefore, there is a need to find promising drugs to cure the patients. As of today, there is no promising and efficient drug is available in the market. Viral infection can be cured by inhibiting the activity of Non-structural protease 3 (nsp3) of Chikungunya virus (CHIKV) and therefore, researchers are working to find the small molecules such as phytochemicals and others to reduce the impact or action of nsp3 of CHIKV. Authors previously reported the multi-component reaction and created a library of 200 molecules. Further, the created molecules were filtered against the nsp3 of CHIKV and performed to determine the relative change in free energy for the formation of the nsp3 of CHIKV-CMPD104 complex at 300 K using molecular dynamics simulations and MM-GBSA calculation. In the present work, there is a need to understand the effect of temperature for the formation of the complex and understand the potential of the CMPD104 against the inhibition of nsp3 of CHIKV. Therefore, molecular dynamics simulations of the complex between the CMPD104 and nsp3 of CHIKV were performed at (300, 325, 350, 375 and 400) K. Further, the MM-GBSA calculation were performed to find the thermodynamic parameters like Delta S, Delta H and Delta G to investigate the formation of CMPD104-nsp3 of CHIKV. It is observed that the relative change in free energy increased with increase in temperature (300 to 400) K, therefore, a decrease in inhibition of nsp3 of CHIKV is concluded. (C) 2021 Elsevier B.V. All rights reserved.