A fast pairwise evaluation of molecular surface area

Abstract A fast and general analytical approach was developed for the calculation of the approximate van der Waals and solvent‐accessible surface areas. The method is based on three basic ideas: the use of the Lorentz transformation formula, a rigid‐geometry approximation, and a single fitting parameter that can be refitted on the fly during a simulation. The Lorentz transformation equation is used for the summation of the areas of an atom buried by its neighboring contacting atoms, and implies that a sum of the buried pairwise areas cannot be larger than the surface area of the isolated spherical atom itself. In a rigid‐geometry approximation we numerically calculate and keep constant the surface of each atom buried by the atoms involved in 1‐2 and 1‐3 interactions. Only the contributions from the nonbonded atoms (1‐4 and higher interactions) are considered in terms of the pairwise approximation. The accuracy and speed of the method is competitive with other pairwise algorithms. A major strength of the method is the ease of parametrization. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 737–745, 2002