The SAAP force field: Development of the single amino acid potentials for 20 proteinogenic amino acids and Monte Carlo molecular simulation for short peptides

Abstract

Molecular simulation by using force field parameters has been widely applied in the fields of peptide and protein research for various purposes. We recently proposed a new all-atom protein force field, called the SAAP force field, which utilizes single amino acid potentials (SAAPs) as the fundamental elements. In this article, whole sets of the SAAP force field parameters in vacuo, in ether, and in water have been developed by ab initio calculation for all 20 proteinogenic amino acids and applied to Monte Carlo molecular simulation for two short peptides. The side-chain separation approximation method was employed to obtain the SAAP parameters for the amino acids with a long side chain. Monte Carlo simulation for Met-enkephalin (CHO-Tyr-Gly-Gly-Phe-Met-NH2) by using the SAAP force field revealed that the conformation in vacuo is mainly controlled by strong electrostatic interactions between the amino acid residues, while the SAAPs and the interamino acid Lennard-Jones potentials are predominant in water. In ether, the conformation would be determined by the combination of the three components. On the other hand, the SAAP simulation for chignolin (H-Gly-Tyr-Asp-Pro-Glu-Thr-Gly-Thr-Trp-Gly-OH) reasonably reproduced a native-like beta-hairpin structure in water although the C-terminal and side-chain conformations were different from the native ones. It was suggested that the SAAP force field is a useful tool for analyzing conformations of polypeptides in terms of intrinsic conformational propensities of the single amino acid units.

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

“…where SAAP is a sum of potential energies (SAAP) for the individual amino acid units, ES and LJ are electrostatic and Lennard-Jones potentials between the amino acid units, and OTHERS is the other correlation term, which is ignored in a current version of SAAPFF. Detailed description of these terms and the simulation program was given previously (see also Supplementary Material available online at http://dx.doi.org/10.1155/2013/407862) [33,34]. Canonical MC simulation using the SAAPFF reasonably reproduced randomly fluctuating conformation of Metenkephalin.…”

“…The conformations are defined by dihedral angles, , , 1 , 2 , and so forth, each with an interval of 15 degrees. In this study, the SAAPFF parameters previously developed [33,34] were improved in the following points.…”

“…First, the parameters for main-chain, Pro, and Val in water, which were obtained in the previous version [34] by single-point calculation with the IEFPCM [65][66][67] solvent model using the structures optimized in vacuo, were replaced with those obtained by geometry optimization in water at the HF/6-31+G(d) level using the IEFPCM model in a Gaussian03 program (rev. E.01) [68].…”

“…A discovery of the similarity between the SAAP in water and the statistical structure of the amino acid residues in folded proteins has prompted us to develop a new force field called SAAP for polypeptide molecules [33,34]. The SAAP force field (SAAPFF) is entirely different from conventional force fields in that a polypeptide is divided to the amino acid units, not to the atomic units, solvent effects are implicitly included in the parameters, and the atomic charges are not constant but variable depending on the conformation of the amino acid units.…”

“…Canonical MC simulation using the SAAPFF reasonably reproduced randomly fluctuating conformation of Metenkephalin. However, for chignolin the SAAP-MC simulation did not afford the native -hairpin structure when the simulation was started from the extended structure [34]. Thus, the previous SAAPFF parameters were a little too rough to be applied for structure prediction of the short peptide.…”