Selective Docking of Pyranooxazoles Against nsP2 of CHIKV Eluted Through Isothermally and Non‐Isothermally MD simulations

Abstract

AbstractSelective docking is a novel concept for drug designing and currently used to find potential inhibitors against a non‐structural polyprotein (nsP2) of the chikungunya virus (CHIKV). Herein, authors designed a library of 200 molecules based on pyranooxazoles and used virtual screening, docking, isothermally and non‐isothermally MD simulations and free energy calculations to get potential candidates. The computational strategy is significant to find the promising inhibitor against this infection. Molecular docking approach is employed to find conformation of inhibitors in the active site of nsP2 of CHIKV. This approach is used to calculate the binding free energy for the drug‐target complex formation by involving various intermolecular interactions i. e. van der Waals, conventional hydrogen bonds, carbon hydrogen bonds etc. Based on binding energy, authors have taken top four candidates for further screening through SWISSADME and Molinspiration. All the four screened molecules obey “Lipinski's Rule of Five” and also gave satisfactory drug likeness values. Later, the top one molecule was taken and studied via isothermally and non‐isothermally MD simulations. MD simulations method was employed to determine change in free energy for the formation of complex between the CMPD167 and nsP2 of CHIKV. Results obtained suggest that CMPD167 is a potential inhibitor against nsP2 of CHIKV.