EXACT AND EFFICIENT ANALYTICAL CALCULATION OF THE ACCESSIBLE SURFACE-AREAS AND THEIR GRADIENTS FOR MACROMOLECULES

A new method for exact analytical calculation of the accessible surfac e areas and their gradients with respect to atomic coordinates is desc ribed. The new surface routine, GETAREA, finds solvent-exposed vertice s of intersecting atoms, and thereby avoids calculating buried vertice s which are not needed to determine the accessible surface area by t:h e Gauss-Bonnet theorem. The surface routine was implemented in FANTOM, a program for energy minimization and Monte Carlo simulation, and tes ted for accuracy and efficiency in extensive energy minimizations of M et-enkephalin, the alpha-amylase inhibitor tendamistat, and avian panc reatic polypeptide (APP). The CPU time for the exact calculation of th e accessible surface areas and their gradients has been reduced by fac tors of 2.2 (Met-enkephalin) and 3.2 (tendamistat) compared with our p revious approach. The efficiency of our exact method is similar to the recently described approximate methods MSEED and SASAD. The performan ce of several atomic solvation parameter sets was tested in searches f or low energy conformations of APP among conformations near the native X-ray crystal structure and highly distorted structures. The protein solvation parameters from Ooi et al. [Proc. Natl. Acad. Sci. USA, 84, 3086 (1987)] and from Wesson and Eisenberg [Prot. Sci., 1, 227 (1992)] showed a good correlation between solvation energies of the conformat ions and their root-mean-square deviations from the X-ray crystal stru cture of APP. (C) 1998 John Wiley & Sons, Inc.