APPLICABILITY OF PM3 TO TRANSPHOSPHORYLATION REACTION-PATH - TOWARD DESIGNING A MINIMAL RIBOZYME

A growing body of evidence shows that RNA can catalyze many of the rea ctions necessary both for replication of genetic material and the poss ible transition into the modern protein-based world. However, contempo rary ribozymes are too large to have self-assembled from a prebiotic o ligonucleotide pool. Still, it is likely that the major features of th e earliest ribozymes have been preserved as molecular fossils in the c atalytic RNA of today. Therefore, the search for a minimal ribozyme ha s been aimed at finding the necessary structural features of a modern ribozyme (Beaudry and Joyce, 1990). Both a three-dimensional model and quantum chemical calculations are required to quantitatively determin e the effects of structural features of the ribozyme on the reaction i t catalyzes. Using this model, quantum chemical calculations must be p erformed to determine quantitatively the effects of structural feature s on catalysis. Previous studies of the reaction path have been conduc ted at the ab initio level, but these methods are limited to small mod els due to enormous computational requirements. Semiempirical methods have been applied to large systems in the past; however, the accuracy of these methods depends largely on the system under investigation. In the preent study we assess the validity of the MNDO/PM3 method on a s imple model of the ribozyme-catalyzed reaction, or hydrolysis of phosp horic acid. We find that the results are qualitatively similar to ab i nitio results using large basis sets. Therefore, PM3 is suitable for s tudying the reaction path of the ribozyme-catalyzed reaction.