Calculations of heavy atom kinetic isotope effect in phosphate monoester hydrolysis

Calculations of heavy atom kinetic isotope effect in phosphate monoester hydrolysis 

Hydrolysis of phosphate esters is one of the fundamental biochemical reactions and a vast amount of research has been devoted to the study of phosphoryl transfer reactions [57-60], both in solution and in enzymes. Despite these efforts there are still ambiguities regarding the interpretation of experimental data (e.g., linear free energy relationships, kinetic isotope effects, crystal structures of enzyme-inhibitor complexes etc.) in terms of detailed reaction mechanisms [21,25,59,60]. Of particular interest has been to determine 

The inclusion of solvent effects using continuum SCRF models does neither provide any significant effect on the geometries of the reactive species (the ionic P-0 bond lengths change by around 0.01-0.02 A) nor on the calculated EIE and KIE values. However, the observed trend demonstrates a small increase in the value of normal EIE related to deprotonation of phosphate. The corresponding small decrease in the KIE of the associative mechanism and increase in value of dissociative mechanism are also found. 

Theoretical Biochemistry - Processes and Properties of Biological Systems Theoretical and Computational Chemistry, Vol. 9 2001 Elsevier Science B.V. All rights reserved 

Monte Carlo simulations of HIV-1 protease binding dynamics and thermodynamics with ensembles of protein conformations incorporating protein flexibility in deciphering mechanisms of molecular recognition 

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