MIAX: a system for assessment of macromolecular interaction. 3) A parallel hybrid GA for flexible protein docking

We propose a parallel hybrid genetic algorithm for flexible protein-protein docking in order to improve the conventional rigid-body models to manipulate protein-protein interactions. The proposed hybrid algorithm is a combination of an evolutionary algorithm with a simulated annealing one, yielding a powerful protein-complex conformation-searching engine. Parallelization of the procedure makes possible to reach high algorithm performance, in both, execution times and size of treated monomers and complexes. Knowledge on side chain flexibility is extracted by means of an exhaustive analysis of crystallographic data on proteins and protein complexes. Results demonstrate the competency of the algorithm since comparison of calculated and crystallographic data accounts for a maximum of 2.5A in RMS difference, including side chain conformation. The system allows routine analysis of this fundamental molecular biology problem important to elucidate bio-macromolecular function in biophysical and biochemical mechanisms involving molecular recognition and interaction, yielding simultaneously clues for designing new proteins and enzymes directed to different purposes.