Grafting of protein-protein binding sites LlANG Shide, XlAO Lan, MA0 Fenglou, JIANG Lin, HAN Yuzhen & LA1 Luhua Institute of Physical Chemistry, Peking University, Beijing 10087 1, China Correspondence should be addressed to Lai Luhua (e-mail: lai@linux2.ipc.pku.edu.cn) Abstract A strategy for grafting protein-protein binding sites is described. Firstly, key interaction residues at the interface of ligand protein to be grafted are identified and suitable positions In scaffold protein for grafting these key residues are sought. Secondly, the scaffold proteins are superposed onto the ligand protein based on the corresponding C , and CB atoms. The complementarity between the scaffold protein and the receptor protein is evaluated and only matches with high score are accepted. The relative position between scaffold and receptor proteins is adjusted so that the interface has a reasonable packing density. Then the scaffold protein is mutated to corresponding residues in ligand protein at each candidate position. And the residues having bad steric contacts with the receptor proteins, or buried charged residues not involved in the formation of any salt bridge are mutated. Finally, the mutated scaffold protein in complex with receptor protein is co-minimized by Charmm. In addition, we deduce a scoring function to evaluate the affinity between mutated scaffold protein and receptor protein by statistical analysis of rigid binding data sets. Keywords: grafting, superposing, geometric complementarity, scoring function, protein engineering. The long-term goal of protein engineering is to de novo design any desired structure and function. However, this remains a big challenge since we do not clearly understand the relationship between Chinese Science Bulletin Vol. 45 No. 18 September 2000