Toward Structure Prediction for Short Peptides Using the Improved SAAP Force Field Parameters

Abstract

Based on the observation that Ramachandran‐type potential energy surfaces of single amino acid units in water are in good agreement with statistical structures of the corresponding amino acid residues in proteins, we recently developed a new all‐atom force field called SAAP, in which the total energy function for a polypeptide is expressed basically as a sum of single amino acid potentials (ESAAP) and electrostatic (EES) and Lennard‐Jones (ELJ) potentials between the amino acid units. In this study, the SAAP force field (SAAPFF) parameters were improved, and classical canonical Monte Carlo (MC) simulation was carried out for short peptide models, that is, Met‐enkephalin and chignolin, at 300 K in an implicit water model. Diverse structures were reasonably obtained for Met‐enkephalin, while three folded structures, one of which corresponds to a native‐like structure with three native hydrogen bonds, were obtained for chignolin. The results suggested that the SAAP‐MC method is useful for conformational sampling for the short peptides. A protocol of SAAP‐MC simulation followed by structural clustering and examination of the obtained structures by ab initio calculation or simply by the number of the hydrogen bonds (or the hardness) was demonstrated to be an effective strategy toward structure prediction for short peptide molecules.