Rational screening in combinatorial peptide libraries of protein functional loop

Redesigning the sequences of protein loops is a frequent practice in protei n design. Based on the new results of protein loop database analysis, a rat ional computer simulation strategy is proposed to obtain functional protein s, which exploits a fast and accurate program to calculate the protein loop conformation, and at the same time, combines molecular docking method with combinatorial chemistry strategy to screen the combinatorial peptide libra ry of protein loops. A characteristic of this method is that it separates t he conformation computation of backbone from that of side chain and incorpo rates side chain growth into the docking procedure and therefore greatly re duces the computation by converting the huge computation on explosive confo rmations to relatively small computation on limited canonical backbone stru ctures and side chain growth. This method can be practically used in screen ing combinatorial peptide libraries of protein loops.