Molecular mechanism of nitrocefin hydrolysis by the L1 metallo-β-lactamase: a benchmark study

Molecular Physics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

Nitrocefin hydrolysis by metallo-β-lactamase is an important model chemical reaction mimicking cephalosporin antibiotic inactivation. Due to the specific chromogenic properties of nitrocefin, transient kinetic data for this available. Despite its importance in understanding mechanism, these can be utilised verify benchmark calculations. This complicated from computational viewpoint as active site carries two double charged cations and therefore highly polarised; nucleophilic attack formation electrophilic should properly described. We calculate Gibbs-free energy profiles three steps comprising entire at QM(DFT)/MM molecular dynamics level. compare results obtained with hybrid functionals differing contribution exact Hartree–Fock exchange, B3LYP-D3, PBE0-D3 BHHLYP-D3. Among them, only calculations performed QM(PBE0-D3)/MM level were able describe intermediate accumulation limiting step. Laplacian electron density maps clarify influence protocol on covalent bond polarisation.

Language: Английский

The Structure and Dynamics of the Enzyme–Substrate Complex of N-Acetylaspartylglutamate Synthase According to the Computer Simulation Data

Moscow University Chemistry Bulletin, Journal Year: 2024, Volume and Issue: 79(4), P. 239 - 245

Published: Aug. 1, 2024

Language: Английский

Towards accurate machine learning predictions of properties of the P–O bond cleaving in ATP upon enzymatic hydrolysis

Mendeleev Communications, Journal Year: 2024, Volume and Issue: 34(6), P. 776 - 779

Published: Nov. 1, 2024

Language: Английский