How does electron exchange correlation influence reactivity of metallo-β-lactamase L1 against cephalosporin antibiotics

• Published in: Chemical physics 2023-02, Vol.566, p.111774, Article 111774
• Main Authors: Levina, Elena, Tsirelson, Vladimir
• Format: Article
• Language: English
• Subjects: Antibiotic resistance; Exchange correlation; Exchange potential; Fermi hole; Fermionic potential; One-electron potentials; Pauli potential; QM/MM
• ISSN: 0301-0104
• DOI: 10.1016/j.chemphys.2022.111774

[Display omitted] •The slow cephalosporin hydrolysis is caused by the highly delocalized N lone pairs.•Simple geometric criteria fail to reflect the reasons of different hydrolysis rates.•Low Fermi hole variability (kinetic exchange correlation) promotes delocalization.•Static and kinetic exchange correlations are compared via one-electron DFT potentials. Cephalosporin hydrolysis by the metallo-β-lactamase L1 is a reaction where electron delocalization in the substrate-protein complex affects the reaction rate: the more cephalosporin lone pairs are localized on the N atom, the higher hydrolysis rates are. We show that high Fermi holevariability is responsible for the stipulation of the electron lone pairs’ localization.One-electron potentials reveal that higher lone pairs’ localization is expressed in the dominance of the static exchange correlation (reflected in theaverage Fermi hole depth) in theN atomvicinity. However, this dominance was found to be defined by the height of the kinetic exchange potential barriers (expressing the Fermi holevariability and the response of the exchange correlation hidden in the kinetic potential to electron density variations), rather than by the features of the static exchange correlation itself. The need to account both static and kinetic exchange correlations for the reliable description of the electron delocalization explains inapplicability of the simple geometric criteria for the chemical bonding study in the considered systems.