title: Energy Analysis of Zn Polycoordination in a Metalloprotein Environment and of the Role of a Neighboring Aromatic Residue. What Is the Impact of Polarization?
abstract: We analyze the intermolecular interaction energies stabilizing the complex of ethanol in the binding site of alcohol dehydrogenase Zn-metalloenzyme (ADH). In this site Zn(II) is ligated by two cysteine and one imidazole residue and by the ethanol substrate. Ethanol is stacked over a phenylalanine residue. The system has been studied by means of SIBFA (Sum of Interactions Between Fragments Ab initio computed) polarizable molecular mechanics (PMM) supplemented by quantum chemical (QC) computations at various levels of theory. The nonadditivities of the QC interaction energies can be traced back by energy-decomposition analyses and are essentially due to polarization, charge-transfer, and electron correlation energies. These contributions can be reproduced by PMM computations. Interestingly, the polarization energy associated with the presence of the benzene ring in the ADH complex is canceled due to many-body/nonadditivity effects. Therefore this ring does not contribute to stabilization prior to including electron correlation/dispersion effects in the QC calculations or in the absence of the PMM dispersion energy contribution. When these effects are taken into account, the stabilization it contributes is in the 3-9 kcal/mol range, reflecting the need for an accurate reproduction of all components of the interaction energy by PMM.
authors.affiliation: Laboratoire de Pharmacochimie Moléculaire et Cellulaire, U648 INSERM, UFR Biomédicale, Université Paris Descartes, 45, rue des Saints-Pères, 75006 Paris, France UPMC Univ Paris 06, UMR 7616, Laboratoire de Chimie Théorique, case courrier 137, 4 place Jussieu, F-75005, Paris, France, and CNRS, UMR 7616, Laboratoire de Chimie Théorique, case courrier 137, 4 place Jussieu, F-75005, Paris, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: de Courcy
authors.affiliation: Laboratoire de Pharmacochimie Moléculaire et Cellulaire, U648 INSERM, UFR Biomédicale, Université Paris Descartes, 45, rue des Saints-Pères, 75006 Paris, France UPMC Univ Paris 06, UMR 7616, Laboratoire de Chimie Théorique, case courrier 137, 4 place Jussieu, F-75005, Paris, France, and CNRS, UMR 7616, Laboratoire de Chimie Théorique, case courrier 137, 4 place Jussieu, F-75005, Paris, France.
authors.forename: Jean-Philip
authors.initials: JP
authors.lastname: Piquemal
authors.affiliation: Laboratoire de Pharmacochimie Moléculaire et Cellulaire, U648 INSERM, UFR Biomédicale, Université Paris Descartes, 45, rue des Saints-Pères, 75006 Paris, France UPMC Univ Paris 06, UMR 7616, Laboratoire de Chimie Théorique, case courrier 137, 4 place Jussieu, F-75005, Paris, France, and CNRS, UMR 7616, Laboratoire de Chimie Théorique, case courrier 137, 4 place Jussieu, F-75005, Paris, France.
authors.forename: Nohad
authors.initials: N
authors.lastname: Gresh