A linear-scaling quantum mechanical investigation of cytidine deaminase

We describe the divide-and-conquer technique for linear-scaling semiempiric al quantum mechanical calculations. This method has been successfully appli ed to study cytidine deaminase. Large-scale simulations were performed for optimizing geometries surrounding the active site of the enzyme and obtaini ng related energetics. The results of the minimizations provide a significa nt complement to experimental efforts and aid in the understanding of the e nzymatic profile of cytidine deaminase. More specifically, we present our p redictions about the structure of the active species and the structure of t he active site for low pH. Finally, we present our results for the structur e of the zinc ion coordination for different substrates which represent poi nts along the reaction profile. In particular, we find that our results for the Zn-S-gamma 132 and the Zn-S-gamma 129 bondlengths yield similar trends compared to x-ray crystallography data as the enzyme structure changes fro m the ground-state to the transition-state analog and from the transition-s tate analog to the product. (C) 1999 Academic Press.