Flexible ligand docking using a robust evolutionary algorithm

A flexible ligand docking protocol based on evolutionary algorithms is investigated. The proposed approach incorporates family competition and adaptive rules to integrate decreasing-based mutations and self-adaptive mutations to act global and local strategies respectively. The method is applied to a dihydrofolate reductase enzyme with the anti-cancer drug methotrexate and two analogues of antibacterial drug trimethoprim. Conformations and orientations close to the crystallographically determined structures are obtained, as well as alternative structures with low energy. Numerical results indicate that the new approach is very robust. The root mean square derivation of the best docked lowest-energy structure with respect to the corresponding crystal structure is 0.67 Angstrom.