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 as global and local search strategies, respectively. The method is applied to a dihydrofolate reductase enzyme with the anticancer drug methotrexate and two analogues of antibacterial drug trimethoprim. Conformations and orientations closed 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 docked lowest-energy structures have root-mean-square derivations ranging from 0.67 to 1.96 Å with respect to the corresponding crystal structures.