Beyond the rotamer library: genetic algorithm combined with the disturbing mutation process for upbuilding protein side-chains

The disturbing genetic algorithm, incorporating the disturbing mutation process into the genetic algorithm flow, has been developed to extend the searching space of side-chain conformations and to improve the quality of the rotamer library. Moreover, the growing generation amount idea, simulating the real situation of the natural evolution, is introduced to improve the searching speed. In the calculations using the pseudo energy scoring function of the root mean squared deviation, the disturbing genetic algorithm method has been shown to be highly efficient. With the real energy function based on AMBER force field, the program has been applied to rebuilding side-chain conformations of 25 high-quality crystallographic structures of single-protein and protein-protein complexes. The averaged root mean standard deviation of atom coordinates in side-chains and veracities of the torsion angles of chi(1) and chi(1) + chi(2) are 1.165 A, 88.2 and 72.9% for the buried residues, respectively, and 1.493 A, 79.2 and 64.7% for all residues, showing that the method has equal precision to the program SCWRL, whereas it performs better in the prediction of buried residues and protein-protein interfaces. This method has been successfully used in redesigning the interface of the Basnase-Barstar complex, indicating that it will have extensive application in protein design, protein sequence and structure relationship studies, and research on protein-protein interaction.