Application of a Distance-Dependent Sigmoidal Dielectric Constant to the REMC/SAAP3D Simulations of Chignolin, Trp-Cage,
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Application of a Distance‑Dependent Sigmoidal Dielectric Constant to the REMC/SAAP3D Simulations of Chignolin, Trp‑Cage, and the G10q Mutant Michio Iwaoka1 · Koji Yoshida1 · Taku Shimosato1 Accepted: 22 October 2020 / Published online: 27 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The replica-exchange Monte Carlo method based on the single amino acid potential (SAAP) force field, i.e., REMC/SAAP3D, was recently developed by our group for the molecular simulation of short peptides. In this study, the method has been improved by applying a distance-dependent dielectric (DDD) constant and extended to the peptides containing d-amino acid (AA) residues. For chignolin (10 AAs), a sigmoidal DDD model reasonably allocated the native-like β-hairpin structure with all-atom root mean square deviation (RMSD) = 2.0 Å as a global energy minimum. The optimal DDD condition was subsequently applied for Trp-cage (20 AAs) and its G10q mutant. The native-like α-rich folded structures with main-chain RMSD = 3.7 and 3.8 Å were obtained as global energy minima for Trp-cage and G10q, respectively. The results suggested that the REMC/SAAP3D method with the sigmoidal DDD model is useful for structural prediction for the short peptides comprised of up to 20 AAs. In addition, the relative contributions of SAAP to the total energy (%SAAP) were evaluated by energetic component analysis. The ratios of %SAAP were about 40 and 20% for chignolin and Trp-cage (or G10q), respectively. It was proposed that SAAP is more important for the secondary structure formation than for the assembly to a higher-order folded structure, in which the attractive van der Waals interaction may play a more important role. Keywords Molecular simulation · SAAP force field · Replica-exchange method · Distance-dependent dielectric · Chignolin · Trp-cage
1 Introduction Molecular simulation techniques are important and fundamental tools in versatile fields of protein and peptide science [1]. Since peptides have also been found to be potential targets of drug discovery [2–4], a demand of the researchers to accurately predict the molecular structures and interactions by molecular simulation is increasing progressively [5–9]. Many force fields have been developed to date for this purpose, such as AMBER [10, 11], CHARMM [12], GROMOS [13], OPLS [14], etc.[15–17]. ECEPP [18, 19], which was developed by Scheraga’s group, is another representative This paper is dedicated to late Dr. Harold A. Scheraga. * Michio Iwaoka [email protected] 1
Department of Chemistry, School of Science, Tokai University, Kitakaname, Hiratsuka‑shi, Kanagawa 259‑1292, Japan
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one, which has greatly contributed to the development of the relevant research areas from the beginning. These force fields are current targets of researchers to improve the accuracy and efficiency [20–24]. In most of such force fields, a peptide molecule is treated as an assembly of atoms. Thus, the inherently complicated potential energy surface (PES) of a
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