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 B-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.
| Original language | English |
|---|---|
| Pages (from-to) | 2158-2172 |
| Number of pages | 15 |
| Journal | Journal of Chemical Theory and Computation |
| Volume | 5 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Aug 2009 |
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ASJC Scopus subject areas
- Physical and Theoretical Chemistry
- Computer Science Applications
Cite this
Ab initio Raman spectra of β-lactamase inhibitor intermediates bound to E166a SHV β-lactamase. / Miani, Andrea; Helfand, Marion Skalweit; Raugei, Simone.
In: Journal of Chemical Theory and Computation, Vol. 5, No. 8, 08.2009, p. 2158-2172.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Ab initio Raman spectra of β-lactamase inhibitor intermediates bound to E166a SHV β-lactamase
AU - Miani, Andrea
AU - Helfand, Marion Skalweit
AU - Raugei, Simone
PY - 2009/8
Y1 - 2009/8
N2 - 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 B-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.
AB - 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 B-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.
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U2 - 10.1021/ct900131q
DO - 10.1021/ct900131q
M3 - Article
VL - 5
SP - 2158
EP - 2172
JO - Journal of Chemical Theory and Computation
JF - Journal of Chemical Theory and Computation
SN - 1549-9618
IS - 8
ER -