DNA Binding Mode and Affinity of Antitumor Drugs of 2-aroylbenzofuran-3-ols: Molecular Dynamics Simulation Study

Abstract

Molecular docking and molecular dynamics (MD) simulations were used for determining the binding positions of 2-aroylbenzofuran-3-ols, which positions cannot be attained from experimental studies. MD simulation was performed for all initial structures docked within 15000 ps. RMSD and potential energy analysis showed that all simulations reach equilibrium after 3000 ps. Analysis of the simulation trajectories showed that the structures of initial docked complexes and equilibrium structures in MD are identical. Moreover, a direct relation between steric hindrance of R² substituent group and binding mode on DNA structure was found. The MM/GBSA analysis showed that the van der Waals (vdW) energy term is the most important energy term in binding process. It has been also found that the vdW and non-polar energy terms (∆G_sur) are favorable for binding. At the same time, the polar groove-binding energy term (∆G_GB) is an unfavorable term in the predicted binding free energy (∆G_binding).