{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T01:59:13Z","timestamp":1775699953819,"version":"3.50.1"},"reference-count":58,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T00:00:00Z","timestamp":1733097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["JP20K06592"],"award-info":[{"award-number":["JP20K06592"]}]},{"name":"JSPS KAKENHI","award":["JP21K06293"],"award-info":[{"award-number":["JP21K06293"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Computation"],"abstract":"<jats:p>Biological phenomena are chemical reactions, which are inherently non-stopping or \u201cflowing\u201d in nature. Molecular dynamics (MD) is used to analyze the dynamics and energetics of interacting atoms, but it cannot handle chemical reactions involving bond formation and breaking. Quantum mechanics\/molecular mechanics (QM\/MM) umbrella sampling MD simulations gives us a significant clue about transition states of chemical reactions and their energy levels, which are the pivotal points in understanding the nature of life. To demonstrate the importance of this method, we present here the results of our application of it to the elucidation of the mechanism of chiral-selective aminoacylation of an RNA minihelix considered to be a primitive form of tRNA. The QM\/MM MD simulation, for the first time, elucidated the \u201cflowing\u201d atomistic mechanisms of the reaction and indicated that the L-Ala moiety stabilizes the transition state more than D-Ala, resulting in L-Ala preference in the aminoacylation reaction in the RNA. The QM\/MM method not only provides important clues to the elucidation of the origin of homochirality of biological systems, but also is expected to become an important tool that will play a critical role in the analysis of biomolecular reactions, combined with the development of artificial intelligence.<\/jats:p>","DOI":"10.3390\/computation12120238","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T13:34:04Z","timestamp":1733146444000},"page":"238","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Quantum Mechanics\/Molecular Mechanics Simulations for Chiral-Selective Aminoacylation: Unraveling the Nature of Life"],"prefix":"10.3390","volume":"12","author":[{"given":"Tadashi","family":"Ando","sequence":"first","affiliation":[{"name":"Department of Applied Electronics, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku 125-8585, Tokyo, Japan"},{"name":"Research Institute for Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Tamura","sequence":"additional","affiliation":[{"name":"Research Institute for Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, Chiba, Japan"},{"name":"Department of Biological Science and Technology, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku 125-8585, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1038\/185416a0","article-title":"Structure of h\u00e6moglobin: A three-dimensional Fourier synthesis at 5.5-\u00c5. resolution, obtained by X-ray analysis","volume":"185","author":"Perutz","year":"1960","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1038\/185422a0","article-title":"Structure of myoglobin: A three-dimensional Fourier synthesis at 2 \u00c5. resolution","volume":"185","author":"Kendrew","year":"1950","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1126\/science.150.3699.979","article-title":"The X-ray analysis of complicated molecules","volume":"150","author":"Hodgkin","year":"1965","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.pbiomolbio.2021.09.002","article-title":"The first resolution revolution in protein structure analysis: X-ray diffraction of polypeptide conformations and globular protein folds in 1950s and 1960s","volume":"167","author":"Blundell","year":"2021","journal-title":"Prog. 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