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Validation of molecular force field parameters for peptides including isomerized amino acids
Author(s) -
Oda Akifumi,
Nakayoshi Tomoki,
Fukuyoshi Shuichi,
Kurimoto Eiji,
Yamaotsu Noriyuki,
Hirono Shuichi,
Takahashi Ohgi
Publication year - 2018
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.22821
Subject(s) - chemistry , tripeptide , amino acid , force field (fiction) , amino acid residue , molecular mechanics , molecular dynamics , computational chemistry , molecule , stereochemistry , organic chemistry , peptide sequence , biochemistry , artificial intelligence , computer science , gene
Recently, stereoinversions and isomerizations of amino acid residues in the proteins of living beings have been observed. Because isomerized amino acids cause structural changes and denaturation of proteins, isomerizations of amino acid residues are suspected to cause age‐related diseases. In this study, AMBER molecular force field parameters were tested by using computationally generated nonapeptides and tripeptides including stereoinverted and/or isomerized amino acid residues. Energy calculations by using density functional theory were also performed for comparison. Although the force field parameters were developed by parameter fitting for l ‐α‐amino acids, the accuracy of the computational results for d ‐amino acids and β‐amino acids was comparable to those for l ‐α‐amino acids. The conformational energies for tripeptides calculated by using density functional theory were reproduced more accurately than those for nonapeptides calculated by using the molecular mechanical force field. The evaluations were performed for the ff99SB, ff03, ff12SB, and the latest ff14SB force field parameters.