A genetic algorithm for the ligand-protein docking problem

Genetics and Molecular Biology

Camila S. De Magalhães²  Hélio J.c. Barbosa²  Laurent E. Dardenne¹ 

[1] ,Laboratório Nacional de Computação Científica Departamento de Matemática Aplicada e Computacional Petrópolis RJ ,Brazil

关键词: ligand-protein docking;    flexible docking;    genetic algorithms;   

DOI  :  10.1590/S1415-47572004000400022

来源: SciELO

【 摘 要 】

We analyzed the performance of a real coded "steady-state" genetic algorithm (SSGA) using a grid-based methodology in docking five HIV-1 protease-ligand complexes having known three-dimensional structures. All ligands tested are highly flexible, having more than 10 conformational degrees of freedom. The SSGA was tested for the rigid and flexible ligand docking cases. The implemented genetic algorithm was able to dock successfully rigid and flexible ligand molecules, but with a decreasing performance when the number of ligand conformational degrees of freedom increased. The docked lowest-energy structures have root mean square deviation (RMSD) with respect to the corresponding experimental crystallographic structure ranging from 0.037 Å to 0.090 Å in the rigid docking, and 0.420 Å to 1.943 Å in the flexible docking. We found that not only the number of ligand conformational degrees of freedom is an important aspect to the algorithm performance, but also that the more internal dihedral angles are critical. Furthermore, our results showed that the initial population distribution can be relevant for the algorithm performance.

【 授权许可】

CC BY   
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