Automated docking of peptides and proteins by using a genetic algorithm combined with a tabu search

A genetic algorithm (GA) combined with a tabu search (TA) has been applied as a minimization method to rake the appropriate associated sites for some biomolecular systems. In our docking procedure, surface complementarity and energetic complementarity of a ligand with its receptor have been consider ed separately in a two-stage docking method. The first stage was to find a set of potential associated sites mainly based on surface complementarity u sing a genetic algorithm combined with a tabu search. This step corresponds with the process of finding the potential binding sites where pharmacophor es will bind. In the second stage, several hundreds of GA minimization step s were performed for each associated site derived from the first stage main ly based on the energetic complementarity. After calculations for both of t he two stages, we can offer several solutions of associated sites for every complex. In this paper, seven biomolecular systems, including five bound c omplexes and two unbound complexes, were chosen from the Protein Data Bank (PDB) to test our method. The calculated results were very encouraging-the hybrid minimization algorithm successfully reaches the correct solutions ne ar the best binded modes for these protein complexes. The docking results n ot only predict the bound complexes very well, but also get a relatively ac curate complexed conformation for unbound systems. For the five bound compl exes, the results show that surface complementarity is enough to find the p recise binding modes, the top solution from the tabu list generally corresp onds to the correct binding mode. For the two unbound complexes, due to the conformational changes upon binding, it seems more difficult to get their correct binding conformations, The predicted results show that the correct binding mode also corresponds to a relatively large surface complementarity score. In these two test cases, the correct solution can be found in the t op several solutions from the tabu list. For unbound complexes, the interac tion energy from energetic complementarity is very important, it can be use d to filter these solutions from the surface complementarity. After the eva luation of the energetic complementarity, the conformations and orientation s close to the crystallographically determined structures are resolved. In most cases, the smallest root mean square distance (r.m.s.d.) from the GA c ombined with TA solutions is in a relatively small region. Our program of a utomatic docking is really a universal one among the procedures used for th e theoretical study of molecular recognition.