Catalytic Descriptors to Investigate Catalytic Power in the Reaction of Haloalkane Dehalogenase Enzyme with 1,2-Dichloroethane

Enzymes play a fundamental role in many biological processes. We present a theoretical approach to investigate the catalytic power of the haloalkane dehalogenase reaction with 1,2-dichloroethane. By removing the three main active-site residues one by one from haloalkane dehalogenase, we found two reactive descriptors: one descriptor is the distance difference between the breaking bond and the forming bond, and the other is the charge difference between the transition state and the reactant complex. Both descriptors scale linearly with the reactive barriers, with the three-residue case having the smallest barrier and the zero-residue case having the largest. The results demonstrate that, as the number of residues increases, the catalytic power increases. The predicted free energy barriers using the two descriptors of this reaction in water are 23.1 and 24.2 kcal/mol, both larger than the ones with any residues, indicating that the water solvent hinders the reactivity. Both predicted barrier heights agree well with the calculated one at 25.2 kcal/mol using a quantum mechanics and molecular dynamics approach, and also agree well with the experimental result at 26.0 kcal/mol. This study shows that reactive descriptors can also be used to describe and predict the catalytic performance for enzyme catalysis.