title: Structure and Raman spectrum of clavulanic acid in aqueous solution.
abstract: The calculation of the vibrational Raman spectrum of enzyme-bound beta-lactamase inhibitors may be of help to understand the mechanisms responsible for bacterial drug resistance. Here, we present a study of the solvation structure and the vibrational properties of clavulanate, an important beta-lactamase inhibitor, in aqueous solution as obtained from full quantum and hybrid empirical/quantum molecular dynamics simulations at ambient conditions. The analysis of the vibrational density of states indicates that hybrid empirical/quantum mechanical simulations are able to properly describe the vibrational levels of clavulanate in solution. In addition, we propose a computationally efficient protocol to calculate the vibrational Raman effect for large solute molecules in water, which is able to faithfully reproduce the experimentally recorded clavulanate Raman spectrum and discloses the possibility to employ hybrid simulations to assign the experimental Raman spectra of inhibitors bound to beta-lactamases.
authors.affiliation: SISSA/ISAS and INFM-DEMOCRITOS, Modeling Center for Research in Atomistic Simulation, via Beirut 2, I-34014, Trieste, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Miani
authors.forename: Simone
authors.initials: S
authors.lastname: Raugei
authors.forename: Paolo
authors.initials: P
authors.lastname: Carloni
authors.forename: Marion S
authors.initials: MS
authors.lastname: Helfand
mesh_terms: D019818:Clavulanic Acid / Q000737:chemistry* / Q000494:pharmacology; D003198:Computer Simulation; D008958:Models, Molecular; D013059:Spectrum Analysis, Raman; D014867:Water / Q000737:chemistry*; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000737:chemistry*
chemical_list: D065093:beta-Lactamase Inhibitors; D014867:Water; D019818:Clavulanic Acid; D001618:beta-Lactamases