Docking and molecular dynamics simulation study of inhibitor 2-Fluoroaristeromycin with anti-malarial drug target PfSAHH

S-adenosyl-l-homocysteine hydrolase of Plasmodium falciparum (PfSAHH) has been reported as a potential drug target against malaria. A series of aristeromycin derivatives and analogs were designed and tested for inhibition of PfSAHH. 2-Fluoroaristeromycin has been reported as a potential inhibitor of PfSAHH. Here, we have performed the molecular dynamics simulation study of 2-Fluoroaristeromycin with PfSAHH with 15-ns simulation time to evaluate the dynamic perturbation of inhibitor in the binding site of PfSAHH in docked complex. This indicates that the complex structure of PfSAHH-2-Fluoroaristeromycin is stable after 10 ns of simulation. MD results indicate that Leu53, His54, Thr56, Glu58, Cys59, Asp134, Glu200, Lys230, Leu389, Leu392, Gly397, Hip398, Met403, and Phe407 are the key residues in the binding pocket of PfSAHH that interacts with the inhibitor 2-Fluoroaristeromycin. Earlier studies have reported Cys59 of PfSAHH as a selective residue to design potential and specific inhibitor of PfSAHH. Simulation study also indicates the role of Cys59 in binding interaction with inhibitor. The MD simulation of PfSAHH-2-Fluoroaristeromycin complex reveals the stable nature of docking interaction. The result provides a set of guidelines for the rational design of potential inhibitors of PfSAHH.