Evaluation of Molecular Docking Using Polynomial Empirical Scoring Functions

Raquel      Dias; Luis Fernando   Saraiva   Macedo Timmers; Rafael   Andrade   Caceres; Walter   Filgueira   de Azevedo Jr.

Abstract

Molecular docking simulations are of pivotal importance for analysis of protein-ligand interactions and also an essential resource for virtual-screening initiatives. In molecular docking simulations several possible docked structures are generated, which create an ensemble of structures representing binary complexes. Therefore, it is crucial to find the best solution for the simulation. One approach to this problem is to employ empirical scoring function to identify the best docked structure. It is expected that scoring functions show a descriptive funnel-shaped energy surface without many false minima to impair the efficiency of conformational sampling. We employed this methodology against a test set with 300 docked structures. Docking simulations of these ligands against enzyme binding pocket indicated a funnel-shaped behavior of the complexation for this system. This review compares a set of recently proposed polynomial empirical scoring functions, implemented in a program called POLSCORE, with two popular scoring function programs (XSCORE and DrugScore). Overall comparison indicated that POLSCORE works better to predict the correct docked position, for the ensemble of docked structures analyzed in the present work.

Keywords: Funnel-shaped energy surface, polynomial empirical scoring functions, virtual screening, protein-ligand, docking, CDK2, enoyl-reductase, purine nucleoside phosphorylase