{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T15:06:42Z","timestamp":1790867202155,"version":"4.1.0"},"reference-count":91,"publisher":"American Chemical Society (ACS)","issue":"39","license":[{"start":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T00:00:00Z","timestamp":1430438400000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000179","name":"NSF Office of the Director","doi-asserted-by":"publisher","award":["IGERT"],"award-info":[{"award-number":["IGERT"]}],"id":[{"id":"10.13039\/100000179","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001677","name":"National institute of Health and Medical Research","doi-asserted-by":"publisher","award":["R01-GM079223"],"award-info":[{"award-number":["R01-GM079223"]}],"id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,10,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Acetylcholinesterase (AChE) is a crucial enzyme in the cholinergic nerve system that hydrolyzes acetylcholine (ACh) and terminates synaptic signals by reducing the effective concentration of ACh in the synaptic clefts. Organophosphate compounds irreversibly inhibit AChEs, leading to irreparable damage to nerve cells. By employing Born\u2013Oppenheimer ab initio QM\/MM molecular dynamics simulations with umbrella sampling, a state-of-the-art approach to simulate enzyme reactions, we have characterized the covalent inhibition mechanism between AChE and the nerve toxin soman and determined its free energy profile for the first time. Our results indicate that phosphonylation of the catalytic serine by soman employs an addition\u2013elimination mechanism, which is highly associative and stepwise: in the initial addition step, which is also rate-limiting, His440 acts as a general base to facilitate the nucleophilic attack of Ser200 on the soman\u2019s phosphorus atom to form a trigonal bipyrimidal pentacovalent intermediate; in the subsequent elimination step, Try121 of the catalytic gorge stabilizes the leaving fluorine atom prior to its dissociation from the active site. Together with our previous characterization of the aging mechanism of soman inhibited AChE, our simulations have revealed detailed molecular mechanistic insights into the damaging function of the nerve agent soman.<\/jats:p>","DOI":"10.1021\/jp502712d","type":"journal-article","created":{"date-parts":[[2014,5,1]],"date-time":"2014-05-01T16:41:28Z","timestamp":1398962488000},"page":"9132-9139","source":"Crossref","is-referenced-by-count":35,"title":["How Is\nAcetylcholinesterase Phosphonylated by Soman?\nAn\n                    <i>Ab Initio<\/i>\n                    QM\/MM Molecular Dynamics Study"],"prefix":"10.1021","volume":"118","author":[{"given":"Gulseher Sarah","family":"Sirin","sequence":"first","affiliation":[{"name":"New York University School of Medicine , , , ,","place":["New York, New York, United States, 10016"]},{"name":"New York University , , , ,","place":["New York, New York, United States, 10003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingkai","family":"Zhang","sequence":"additional","affiliation":[{"name":"New York University , , , ,","place":["New York, New York, United States, 10003"]},{"name":"NYU-ECNU Center for Computational Chemistry at NYU Shanghai , ,","place":["Shanghai, China, 200062"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,5,1]]},"reference":[{"key":"2026090219290465300_cit1","first-page":"103","article-title":"Acetylcholinesterase","volume":"43","author":"Rosenberry","year":"2006","journal-title":"Adv. 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