Validation of molecular force field parameters for peptides including isomerized amino acids |
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| Authors: | Akifumi Oda Tomoki Nakayoshi Shuichi Fukuyoshi Eiji Kurimoto Noriyuki Yamaotsu Shuichi Hirono Ohgi Takahashi |
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| Institution: | 1. Faculty of Pharmacy, Meijo University, Nagoya, Aichi, Japan;2. Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan;3. Institute for Protein Research, Osaka University, Osaka, Japan;4. School of Pharmacy, Kitasato University, Tokyo, Japan;5. Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, Japan |
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| Abstract: | 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. |
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| Keywords: | d‐amino acid density functional theory force field molecular mechanics β ‐amino acid |
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