Molecular modeling and prediction of binding mode and relative binding affinity of Art-Qui-OH with P. falciparum Histo-Aspartic Protease (HAP)

Abstract

The relative binding affinity in terms of ΔΔG (bind-cald) value of the antimalarial compound artemisinin-quinine hybrid is primarily derived and is discussed in this article with reference to the ΔG (bind-cald) values of two known inhibitors Pepstatin-A and KNI-10006 complexed with HAP enzyme. The ΔG (bind-cald) value for KNI-10006 and Pepstatin-A is -14.10 kcal/mol and -13.09 kcal/mol respectively. The MM-GB/SA scoring results in the relative binding energy (ΔΔG (bind-cald)) of the hybrid molecule with respect to Pepstatin-A as 2.43 kcal/mol and 3.44 kcal/mol against KNI-10006. The overall binding mode of Art-Qui-OH resembles that of Pepstatin-A binding in HAP active site. We suggest here that the ΔΔG (bind-cald) value & proposed binding mode of the Art-Qui-OH for HAP enzyme should be considered for further structure-based drug design effort.