Linear scaling molecular orbital calculations of biological systems using the semiempirical divide and conquer method

A "linear-scaling revolution" is occurring in quantum chemistry. This devel opment is allowing for the first time the routine examination of large mole cular assembles (e.g., proteins and DNA in water) using electronic structur e methods. One of these approaches is the divide and conquer method and, in this article, we review the implementation of this approach for semiempiri cal Hamiltonians. This is then followed by brief reviews of three applicati on areas. First, we will discuss the charge distribution of biological mole cules in solution as described by quantum mechanics. In particular, the rol e polarization and charge transfer plays in affecting the charge distributi on of proteins will be discussed. Next, we will examine the energetic conse quences of charge transfer and polarization on biomolecular solvation. The final section will describe the computation of solvation free energies usin g a combined divide and conquer/Poisson-Boltzmann approach. The application of linear scaling quantum mechanical methods to biology is only just begin ning, but the future is very bright, and it is our opinion that quantum mec hanics will have a profound influence on our understanding of biological sy stems in the coming years. (C) 2000 John Wiley & Sons, Inc.