Rational screening in combinatorial peptide libraries of protein functional loop

Redesigning the sequences of protein loops is a frequent practice in protein design. Based on the new results of protein loop database analysis, a rational computer simulation strategy is proposed to obtain functional proteins, 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 library of protein loops. A characteristic of this method is that it separates the conformation computation of backbone from that of side chain and incorporates side chain growth into the docking procedure and therefore greatly reduces the computation by converting the huge computation on explosive conformations to relatively small computation on limited canonical backbone structures and side chain growth. This method can be practically used in screening combinatorial peptide libraries of protein loops.