Computational Insights for Interactions between nsP2 and nsP3 of CHIKV and Hormones through DFT Computations and Molecular Dynamics Simulations

Abstract

The non‐structural protein (nsP2 & nsP3) of the CHIKV is responsible for the transmission of viral infection. The main role of nsp is involved in the transcription process at an early stage of the infection. In this work, authors have studied the impact of nsP2 and nsP3 of CHIKV on hormones present in the human body using a computational approach. The ten hormones of chemical properties such as 4‐Androsterone‐2,17‐dione, aldosterone, androsterone, corticosterone, cortisol, cortisone, estradiol, estrone, progesterone and testosterone were taken as a potency. From the molecular docking, the binding energy of the complexes is estimated, and cortisone was found to be the highest negative binding energy (‐6.57 kcal/mol) with the nsP2 protease and corticosterone with the nsP3 protease (‐6.47 kcal/mol). This is based on the interactions between hormones and NsP2/NsP3, which are types of noncovalent intermolecular interactions categorized into three types: electrostatic interactions, van der Waals interactions, and hydrogen‐bonding. To validate the docking results, molecular dynamics simulations and MM‐GBSA methods were performed. The change in enthalpy, entropy, and free energy were calculated using MM‐GBSA methods. The nsP2 and nsP3 protease of CHIKV interact strongly with the cortisone and corticosterone with free energy changes of ‐20.55 & ‐36.08 kcal/mol, respectively.