Program

P.28 -- Poster, IWTCP-3

Date: Wednesday, 29 July 2015

Time: 08h30 - 10h00

A New Method for Determination of Optimal Pulling Direction for ligand from Binding Pocket: Application to Ranking Binding Affinity by Steered Molecular Dynamics

Quan Van Vuong (1), Tin Trung Nguyen(1), Mai Suan Li (1,2)

(1) Institute for Computational Sciences and Technology, Ho Chi Minh City, Vietnam; (2) Institute of Physics, Polish Academy of Sciences, Warsaw, Poland

In this contribution we present a new method for finding the optimal path to pull ligand from the binding pocket using steered molecular dynamics (SMD). Scoring function is defined as the steric hindrance caused by receptor to ligand movement. Then the optimal path corresponds to minimum of the scoring function. We call the new method SMDA (SMD assisted) because SMD simulation is applied to navigate optimal direction. Contrary to existing navigation methods, our approach takes into account geometry of ligand while other methods including CAVER consider ligand as sphere with a given radius. Using three different target+receptor sets, we have shown that the rupture force $F_{\textrm{max}}$ and non-equilibrium work $ W_{pull} $ obtained by SMDA method show much higher correlation with experimental data on inhibition constants compared to CAVER. Furthermore, $ W_{pull} $ was found to be a better indicator for binding affinity than $F_{\textrm{max}}$. Thus, new SMDA method is a reliable tool for obtaining the best direction for ligand exciting from the binding site. Its combination with the standard SMD technique can provide reasonable results for ranking binding affinities using $ W_{pull} $ as a scoring function.

Presenter: Vuong Van Quan