title: Quantum simulations of the structure and binding of glycopeptide antibiotic aglycons to cell wall analogues.
abstract: The recent rise of vancomycin-resistant enterococci (VRE) and vancomycin-resistant Staphylococcus aureus (VRSA) has given new impetus to the study of the binding between glycopeptide antibiotics and bacterial cell wall termini. Here, we report on an extensive first principles investigation of the binding of vancomycin, avoparcin, teicoplanin, and ristocetin aglycons with dipetides, Ac-d-Ala-X, where X = d-Lac and d-Ser (characteristic of VREs) and X = d-Ala, Gly (characteristic of non-VREs), and a model "methylated d-Ala" CH(2)CH(CH(3))COO(-), in liquid as well as gas phase. The gas-phase ordering of the binding, from strongest to weakest, is Gly, d-Ala, d-Ser, CH(2)CH(CH(3))COO(-), and d-Lac. Calculations show that the order of the Gly and d-Ala binding is reversed in solution. The results are in good agreement with recent experimental findings.
authors.affiliation: Center for High Performance Simulations (CHiPS) and Department of Physics, North Carolina State University, Raleigh, NC 27695-8202, USA.
authors.forename: Jung-Goo
authors.initials: JG
authors.lastname: Lee
authors.forename: Celeste
authors.initials: C
authors.lastname: Sagui
authors.forename: Christopher
authors.initials: C
authors.lastname: Roland
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002473:Cell Wall / Q000378:metabolism*; D003198:Computer Simulation; D004151:Dipeptides; D024881:Drug Resistance, Bacterial; D006020:Glycopeptides / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D011789:Quantum Theory; D013211:Staphylococcus aureus / Q000187:drug effects; D014640:Vancomycin / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D004151:Dipeptides; D006020:Glycopeptides; D014640:Vancomycin