AN IMPROVED ALGORITHM FOR THE ANALYTICAL COMPUTATION OF SOLVENT-EXCLUDED VOLUME - THE TREATMENT OF SINGULARITIES IN SOLVENT-ACCESSIBLE SURFACE-AREA AND VOLUME FUNCTIONS

An algorithm for the analytical computation of solvent-excluded volume is presented as part of our efforts to develop an improved computatio nal model for a solvent effect term, in which the work required to cre ate a cavity in the solvent is expressed as a function of the solvent- excluded volume. In this article we describe mathematical developments in the analytical integration of solvent-accessible surface (SAS) are a, the singularities in SAS area and volume functions, and the procedu res required to detect and treat singularities. Techniques to increase algorithm performance are presented, which improve computational spee d by about five times, on the average. The accuracy of the analytical method for volume computation is compared with the accuracy of two num erical methods: the numerical integration of SAS area and the point-by -point scanning method. This algorithm calculates the volume of the sp heres confined among their intersection planes and resembles a numeric al integration of surface area by summing up volume layers. These char acteristics make the algorithm useful in analytically calculating the work required to create a convex cavity in a solvent and the work (p D elta V) associated with a change in the solvent-excluded volume of the solute due to solvent pressure. (C) 1995 by John Wiley and Sons, Inc.