Development of SAAP3D force field and the application to replica-exchange Monte Carlo simulation for chignolin and C-peptide

Single amino acid potential (SAAP) would be a prominent factor to determine peptide conformations. To prove this hypothesis, we previously developed SAAP force field for molecular simulation of polypeptides. In this study, the force field was renovated to SAAP3D force field by applying more accurate...

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Bibliographic Details
Published in:Journal of computer-aided molecular design 2017-12, Vol.31 (12), p.1039-1052
Main Authors: Iwaoka, Michio, Suzuki, Toshiki, Shoji, Yuya, Dedachi, Kenichi, Shimosato, Taku, Minezaki, Toshiya, Hojo, Hironobu, Onuki, Hiroyuki, Hirota, Hiroshi
Format: Article
Language:English
Subjects:
Amino acids
Animal Anatomy
C-Peptide - chemistry
Chains
Chemistry
Chemistry and Materials Science
Cluster analysis
Clustering
Computer Applications in Chemistry
Computer Simulation
Histology
Imidazole
Models, Molecular
Monte Carlo Method
Monte Carlo simulation
Morphology
NMR
Nuclear magnetic resonance
Oligopeptides - chemistry
Peptides
Physical Chemistry
Polypeptides
Protein Conformation
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Summary:Single amino acid potential (SAAP) would be a prominent factor to determine peptide conformations. To prove this hypothesis, we previously developed SAAP force field for molecular simulation of polypeptides. In this study, the force field was renovated to SAAP3D force field by applying more accurate three-dimensional main-chain parameters, instead of the original two-dimensional ones, for the amino acids having a long side-chain. To demonstrate effectiveness of the SAAP3D force field, replica-exchange Monte Carlo (REMC) simulation was performed for two benchmark short peptides, chignolin (H-GYDPETGTWG-OH) and C-peptide (CHO-AETAAAKFLRAHA-NH 2 ). For chignolin, REMC/SAAP3D simulation correctly produced native β-turn structures, whose minimal all-atom root-mean-square deviation value measured from the native NMR structure (except for H) was 1.2 Å, at 300 K in implicit water, along with misfolded β-hairpin structures with unpacked aromatic side chains of Tyr2 and Trp9. Similar results were obtained for chignolin analog [G1Y,G10Y], which folded more tightly to the native β-turn structure than chignolin did. For C-peptide, on the other hand, the α-helix content was larger than the β content on average, suggesting a significant helix-forming propensity. When the imidazole side chain of His12 was protonated (i.e., [His12Hip]), the α content became larger. These observations as well as the representative structures obtained by clustering analysis were in reasonable agreement not only with the structures of C-peptide that were determined in this study by NMR in 30% CD 3 CD in H 2 O at 298 K but also with the experimental and theoretical behaviors having been reported for protonated C-peptide. Thus, accuracy of the SAAP force field was improved by applying three-dimensional main-chain parameters, supporting prominent importance of SAAP for peptide conformations.
ISSN:0920-654X
1573-4951
DOI:10.1007/s10822-017-0084-8