Theoretical and Computational Research on Halide Ion Release Channel of Haloalcohol Dehalogenase From <i>Agrobacterium Radiobacter</i> AD1

Abstract

ABSTRACT Haloalcohol dehalogenases catalyze the dehalogenation of halohydrins through an intramo-lecular nucleophilic displacement. These enzymes exhibit a huge potential in the synthesis of chiral pharmaceutical intermediates. The three types of haloalcohol dehalogenases, A, B and C can catalyze the reversible dehalogenation reaction. Up-to-date studies suggested that the rate-limiting step of the catalysis process of HheC is the release of halide ions and thus ion release channels are assumed to exist. This article includes pure theoretical and computational studies using classic molecular dynamics simulations, random acceleration molecular dy-namics simulations and specialized toolkit MOLE 2.0 for predicting potential ion release channels. After comprehensive analysis of the computational results, the author found out some sites of interest that might be parts of hypothetical channels; but in order to completely investigate the effects of these key residues to the ion release channels, the author raised some assumptions and recommended some mutation strategies for bench scale experimental re-search for validation and further studies.