The binding of protein with its ligand can be generalized into two major modes: direct binding with surface loops or binding associated with hinge movement. Two different strategies were developed to study the conformational variation in the binding process. For directive loop binding, a combinatorial conformational library for the backbone structure of the loop was built up, which includes all possible sub- stable conformations of the loop during the binding procedure. The library of conformations was subject to screening by rigid docking. The streptavidin complex was used as an example to explore the possibility to build the combinatorial conformational library of loop backbone. For hinge binding movement, step-by-step docking method has been proposed and applied to HIV-1 protease and inhibitor system. The results show that both methods can simulate the conformational variation of proteins in the binding process successfully. The proposed methods for studying the binding process of protein and ligand will be helpful for protein and drug design.

Key words: PROTEIN, CONFORMATION, LIGANDS