{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:31:06Z","timestamp":1760059866720,"version":"build-2065373602"},"reference-count":45,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T00:00:00Z","timestamp":1752624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K15244"],"award-info":[{"award-number":["21K15244"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The deamidation rate is relatively high for Asn residues with Phe as the C-terminal adjacent residue in \u03b3S-crystallin, which is one of the human crystalline lens proteins. However, peptide-based experiments indicated that bulky amino acid residues on the C-terminal side impaired Asn deamination. In this study, we hypothesized that the side chain of Phe affects the Asn deamidation rate and investigated the succinimide formation process using quantum chemical calculations. The B3LYP density functional theory was used to obtain optimized geometries of energy minima and transition states, and MP2 and M06-2X calculations were used to obtain the single-point energy. Activation barriers and rate-determining step changed depending on the orientation of the Phe side chain. In pathways where an interaction occurred between the benzene ring and the amide group of the Asn residue, the activation barrier was lower than in pathways where this interaction did not occur. Since the aromatic ring is oriented toward the Asn side in experimentally determined structures of \u03b3S-crystallin, the above interaction is considered to enhance the Asn deamidation.<\/jats:p>","DOI":"10.3390\/ijms26146819","type":"journal-article","created":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T12:55:00Z","timestamp":1752670500000},"page":"6819","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigation of the Effect of C-Terminal Adjacent Phenylalanine Residues on Asparagine Deamidation by Quantum Chemical Calculations"],"prefix":"10.3390","volume":"26","author":[{"given":"Koichi","family":"Kato","sequence":"first","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Shonan University of Medical Sciences, 16-10 Kamishinano, Totsuka-ku, Yokohama 244-0806, Japan"},{"name":"Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7627-0523","authenticated-orcid":false,"given":"Haruka","family":"Asai","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Aichi Medical University, 1-1 Yazakokarimata, Nagakute 480-1195, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2905-3611","authenticated-orcid":false,"given":"Tomoki","family":"Nakayoshi","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan"},{"name":"Institute for Advanced Research, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-0814, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayato","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akifumi","family":"Oda","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan"},{"name":"Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita 565-0871, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshinobu","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Shonan University of Medical Sciences, 16-10 Kamishinano, Totsuka-ku, Yokohama 244-0806, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.pbiomolbio.2003.11.012","article-title":"Ageing and Vision: Structure, Stability and Function of Lens Crystallins","volume":"86","author":"Lubsen","year":"2004","journal-title":"Prog. 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