title: Ab Initio Raman Spectra of β-Lactamase Inhibitor Intermediates Bound to E166A SHV β-Lactamase.
abstract: The assignment and the analysis of the experimental vibrational Raman spectra of enzyme bound β-lactamase inhibitors may be of help to understand the mechanisms responsible for bacterial drug resistance. We present a computational study of the structural and vibrational properties of clavulanic acid and tazobactam intermediates, two important β-lactamase inhibitors, bound to the singly mutated E166A SHV β-lactamase in aqueous solution by hybrid molecular mechanics/quantum mechanics (QM/MM) simulations at ambient conditions. We compare the Raman spectra obtained from the time autocorrelation function of polarizability tensor as obtained from a QM/MM protocol to those obtained from the instantaneous normal modes analysis performed on top of the QM/MM trajectory in order to establish the accuracy of these two computational methods and to review the previously made assignments. It is shown that the O═C-C═C-NH- trans-enamine moiety symmetric and asymmetric stretchings are strongly coupled with the N-H in-plane rocking and originate the band structure between 1600 cm(-1) and 1640 cm(-1). Results indicate also that to properly describe Raman scattering properties of the trans-enamine intermediate, it is crucial to include both mechanical (beyond the second derivative of the potential energy at equilibrium) and electrical (beyond the first derivative of polarizability) anharmonicity. In addition, we show that the environment electrostatic field dynamically modulates the Raman activity, enhancing or inhibiting it.
authors.affiliation: SISSA and INFM-DEMOCRITOS center via Beirut 2, I-34014, Trieste, Italy, and Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio 44106.
authors.forename: Andrea
authors.initials: A
authors.lastname: Miani
authors.affiliation: SISSA and INFM-DEMOCRITOS center via Beirut 2, I-34014, Trieste, Italy, and Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio 44106.
authors.forename: Marion Skalweit
authors.initials: MS
authors.lastname: Helfand
authors.affiliation: SISSA and INFM-DEMOCRITOS center via Beirut 2, I-34014, Trieste, Italy, and Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio 44106.
authors.forename: Simone
authors.initials: S
authors.lastname: Raugei