A Study of the Mechanism of Ribonuclease-S Using CNDO/2 Electronic Structure Calculations

Bovine Pancreatic Ribonuclease-S hydrolzes RNA molecules in a two step mechanism: 1. transphosphorylation, and 2. hydrolysis. The mechanism of the enzyme is studied using a model substrate for RNA, 2-hydroxyethyl methyl phosphate union. Electronic structure calculations are done at the CNDO/2 level, using the CININ optimization routine to minimize geometries. Two possible reaction paths are plotted for each step of the reaction, with the lowest activation energy path assumed to be the one taken by RNA. CNDO/2 results, however, yield negative activation anaeroles, a physically impossible result