Linear-scaling quantum mechanical calculations of biological molecules: The divide-and-conquer approach

The divide-and-conquer technique for linear-scaling quantum mechanical calculations is reviewed. The method divides a large system into many subsystems, determines the density matrix of each subsystem separately, and sums the corresponding subsystem contributions to obtain the total density matrix and the energy of the system. There is a uniform chemical potential to allow transfer of electrons between subsystems and to insure the normalization of the electron density. The implementation of the method for semiempirical quantum chemistry Hamiltonians is described. The review describes the application to the study of the catalytic mechanisms of cytidine deaminase, an enzyme which accelerates the rate of hydrolytic deamination of cytidine to uridine. The linear-scaling quantum mechanical calculations determined the active species of the ground-state complex and the structure of the reaction transition-state analog complex. (C) 1998 Elsevier Science B.V. All rights reserved.