Importance of Lone Pair Interactions/Redistribution in Hard and Soft Ligands within the Active Site of Alcohol Dehydrogenase Zn-metalloenzyme: Insights from Electron Localization Function

摘要

As a continuation of our previous work (de Courcy et al., 2008. J. Chem. Theo. Comput. 4 1659), lone pair-cation interactions were quantum-mechanically studied within the active site of the alcohol dehydrogenase Zn(II)-metalloenzyme by means of the topological analysis of the Electron Localization Function (ELF) and the Reduced Variational Space (RVS) energy decomposition analysis. Ligands lone pairs in direct interaction with the metal were shown to control the physical nature of the interaction asit appears to be dominated by polarization when the number of interacting lone pairs increases. Furthermore, we observed a peculiar behaviour of the cysteinate S~- lone pairs which can redistribute and merge, thereby reducing their number to accommodatethe zinc cation which also exhibits a consequent plasticity of its density outer shells which can delocalize towards ligands. Such observations should allow a deeper understanding of the usual softness/hardness concept of ions and ligands.