Analysis of the Interactions Taking Place in the Recognition Site of a Bimetallic Mg(II)-Zn(II) Enzyme, Isopentenyl Diphosphate Isomerase. A Parallel Quantum-Chemical and Polarizable Molecular Mechanics Study

作者：Gresh Nohad^*; Audiffren Nicole; Piquemal Jean Philip; de Ruyck Jerome; Ledecq Marie; Wouters Johan

来源：Journal of Physical Chemistry B, 2010, 114(14): 4884-4895.

DOI：10.1021/jp907629k

Using the SIBFA polarizable molecular mechanics procedure, we analyze the binding energy of a bimetallic Mg(II)/Zn(II) enzyme, isopentenyl diphosphate isomerase, to an inhibitor built up of a trianionic diphosphate and of a cationic ethyldimethylammonium (EDMA) moiety. The analyses are performed on the protein recognition site, which totals 13 residues, as well as on some "mutants" in which one selected residue is removed at a time. They are also carried out for the individual recognition sites, namely, EDMA, Mg(II), and Zn(II). Comparisons are done with ab initio quantum chemistry (QC) results on all considered sites, with different basis sets and at different levels of correlation. The SHWA computations reproduce the evolutions of the QC interaction energies in the recognition site and its "mutants". For such sites, small (<2-3%) relative errors are found after the BSSE correction is done. Such dose agreements can conceal, however. some shortcomings found in the individual binding sites, which QC energy decomposition analyses can identify.

• 出版日期2010-4-15