Computer-aided model-building strategies for protein design

Abstract

Model-building strategies for protein modification and design are developed. These strategies emphasize simple geometric aspects of protein structure, use local coordinate systems defined at particular residues, and systemically consider a large number of alternative sequences and conformations. We have written a computer program, PROTEUS, to implement these search methods. PROTEUS has been used to find positions where disulfide bonds could be added to the N-terminal domain of the .lambda. repressor and to predict how a loop on the surface of repressor could be shortened.