Development of a zoned genetic algorithm for semi-flexible protein-ligand docking in drug design

Abstract

This paper deals with the development of a computational algorithm for semi-flexible protein-ligand docking. For this aim, we developed a methodology in four stages. In the first one, a selection of the test set was carried out. This step was performed with a set of protein-ligand complexes containing both high-resolution and variability of possible structures. In the second one, important aspects of a Molecular Docking Process were selected. In the third one, a zoned Genetic Algorithm and energy computations, using an energy function based on the AMBER force field, were carried out. Finally, verification and validation of obtained results in molecular docking simulations were performed. Accuracy outputs of complex structures obtained in the simulations was assessed by computations of the Root Mean Square Deviation (RMSD) values between the resulting structure and the protein crystal one. Finally, obtained results in the docking simulations were satisfactory and achieved values of RMSD lower than 3 A.