{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T02:45:15Z","timestamp":1793673915573,"version":"4.5.1"},"reference-count":46,"publisher":"American Chemical Society (ACS)","issue":"1","license":[{"start":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T00:00:00Z","timestamp":1608595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_ccbyncnd_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM116130"],"award-info":[{"award-number":["GM116130"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006151","name":"Basic Energy Sciences","doi-asserted-by":"publisher","award":["DE-SC0019327"],"award-info":[{"award-number":["DE-SC0019327"]}],"id":[{"id":"10.13039\/100006151","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Vancomycin is a glycopeptide antibiotic produced by Amycolaptopsis orientalis used to treat serious infections by Gram-positive pathogens including methicillin-resistant Staphylococcus aureus. Vancomycin inhibits cell wall biosynthesis by targeting lipid II, which is the membrane-bound peptidoglycan precursor. The heptapeptide aglycon structure of vancomycin binds to the d-Ala-d-Ala of the pentapeptide stem structure in lipid II. The third residue of vancomycin aglycon is asparagine, which is not directly involved in the dipeptide binding. Nonetheless, asparagine plays a crucial role in substrate recognition, as the vancomycin analogue with asparagine substituted by aspartic acid (VD) shows a reduction in antibacterial activities. To characterize the function of asparagine, binding of vancomycin and its aspartic-acid-substituted analogue VD to l-Lys-d-Ala-d-Ala and l-Lys-d-Ala-d-Lac was investigated using molecular dynamic simulations. Binding interactions were analyzed using root-mean-square deviation (RMSD), two-dimensional (2D) contour plots, hydrogen bond analysis, and free energy calculations of the complexes. The analysis shows that the aspartate substitution introduced a negative charge to the binding cleft of VD, which altered the aglycon conformation that minimized the repulsive lone pair interaction in the binding of a depsipeptide. Our findings provide new insight for the development of novel glycopeptide antibiotics against the emerging vancomycin-resistant pathogens by chemical modification at the third residue in vancomycin to improve its binding affinity to the d-Ala-d-Lac-terminated peptidoglycan in lipid II found in vancomycin-resistant enterococci and vancomycin-resistant S. aureus.<\/jats:p>","DOI":"10.1021\/acsomega.0c05353","type":"journal-article","created":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T04:38:51Z","timestamp":1608611931000},"page":"775-785","source":"Crossref","is-referenced-by-count":22,"title":["Molecular Dynamics Simulation of Atomic Interactions\nin the Vancomycin Binding Site"],"prefix":"10.1021","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5987-1172","authenticated-orcid":true,"given":"Olatunde P.","family":"Olademehin","sequence":"first","affiliation":[{"name":"Baylor University , , , ,","place":["Waco, Texas, United States, 76798"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2007-6606","authenticated-orcid":true,"given":"Sung Joon","family":"Kim","sequence":"additional","affiliation":[{"name":"Howard University , , , ,","place":["Washington, District of Columbia, United States, 20059"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8452-2302","authenticated-orcid":true,"given":"Kevin L.","family":"Shuford","sequence":"additional","affiliation":[{"name":"Baylor University , , , ,","place":["Waco, Texas, United States, 76798"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,12,22]]},"reference":[{"key":"2026090318125459400_cit1","first-page":"606","article-title":"Vancomycin, a new antibiotic. 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