Hydrolysis of cyclic phosphates by ribonuclease A: a computational study using a simplified ab initio quantum model.

The second step in the enzyme-catalyzed hydrolysis of phosphate esters by ribonuclease A (RNase A) was studied using an ab initio quantum-based model of the active site including constrained parts of three critical residues, His-12, His-119, and Lys-41, and a small substrate. The competition between release of the cyclic phosphate intermediate and subsequent hydrolysis following transphosphorylation was explored to determine the electronic factors that contribute to preferential intermediate product release observed experimentally. The structural and energetic results obtained at both the RHF and MP2 levels reveal several contributing factors consistent with experimental observation.