Ab initio study of the reaction mechanism of ribonuclease A with cytidyl-3',5 '-adenosine. I. Geometry optimization of cytidyl-3 ',5 '-adenosine

As a first part of the ab initio study of the reaction mechanism of ribonuc lease A with cytidyl-3',5'-adenosine, the geometry of the cytidyl-3',5'-ade nosine substrate has been optimized using the Hartree-Fock method. Eleven d ifferent starting structures of cytidyl-3',5'-adenosine have been studied. To guarantee a proper alignment with the active site of the ribonuclease A enzyme, a part of the substrate was fixed during the geometry optimization The geometry and intramolecular interactions of the refined conformations h ave been evaluated and two possible prototype structures have been proposed . One of these prototypes is more in accordance with the results of a molec ular dynamics simulation and is therefore presented as a model for the geom etry of cytidyl-3',5'-adenosine in the initial step of the reaction with ri bonuclease A. (C) 1999 John Wiley & Sons, Inc.