Fast, approximate algorithm for detection of solvent-inaccessible atoms

Up to about half of the atoms in biopolymers are inaccessible to solvents. If such atoms can be rapidly identified, time can be saved in the subsequen t computation of atomic surface areas. A quick, approximate method, termed buried atom elimination (BAE), was developed for the detection of such atom s. Following the literature, the method makes use of a Gaussian function to calculate the neighbor density in four tetrahedral directions in 3-dimensi onal space, sometimes twice with different orientations. In macromolecules, our method detects between 63 and 81% of the buried at-ems but also incorr ectly classifies 2-8% of the exposed atoms as buried. These misidentified a toms all have small solvent-exposed (accessible) surface areas (SASAs): the ir surfaces sum to a maximum of 0.5% of the molecular SASA, and their maxim um atomic SASA is 5.1 Angstrom(2). Using our recently reported LCPO method for computing atomic surfaces, which is one of the fastest available, the u se of BAE increases the overall speed of computing the atomic SASAs by a fa ctor of up to 1.6 for surfaces only and 1.9 when first and second derivativ es are computed. BAE decreases the LCPO average absolute atomic error from about 2.3 Angstrom(2) to about 1.7 Angstrom(2) (average for larger compound s). BAE was introduced into the MacroModel molecular modeling package and t ests show that it increases the efficiency of first- and second-derivative energy minimizations and molecular dynamics simulations without adversely a ffecting the stability or accuracy of the calculations. BAE parameters were developed for the most important atom types in biopolymers, based on a par ameterization set of 18 compounds of different size (33-4346 atoms) and cla ss (organics, proteins, DNA, and various complexes), consisting of a total of 23,186 atoms. (C) 1999 John Wiley & Sons, Inc.