A FAST AND SPACE-EFFICIENT BOUNDARY-ELEMENT METHOD FOR COMPUTING ELECTROSTATIC AND HYDRATION EFFECTS IN LARGE MOLECULES

At present, there are two widely used approaches for computing molecul ar hydration and electrostatic effects within the continuum approximat ion: the finite difference method, in which the electric potential is directly computed on a cubic grid, and the induced polarization charge or boundary element method, in which an induced charge distribution i s first computed on the molecular surface and in which solvation effec ts are then calculated by reference to the reaction field arising from this induced surface charge. While the induced surface charge approac h has a number of advantages over finite differences, especially in th e computation of hydration forces and solvent stabilization, the appli cations of this technique have been largely restricted to small molecu les. This is primarily due to the very large system of equations that results when the surface of a macromolecule is discretized into elemen ts small enough to ensure an acceptable level of numerical accuracy wi thin the continuum model. This article describes a new algorithm for i mplementing boundary element calculations within the continuum model. The essence of our approach is only to compute explicitly those intera ctions between surface elements that are relatively close together and to approximate long-range interactions by grid-based multipole expans ion. The resulting system of equations has a relatively sparse coeffic ient matrix and requires disk storage that increases linearly with mol ecular surface area. The technique has numerous applications in the an alysis of solvation effects in large molecules, especially in the area of conformational analysis, where it is critical to accurately estima te the global hydration energy for the entire structure. (C) 1996 by J ohn Wiley & Sons, Inc.