SIMS: Computation of a smooth invariant molecular surface

SIMS, a new method of calculating a smooth invariant molecular dot surface, is presented. The SIMS method generates the smooth molecular surface by rolling two probe spheres. A solvent probe sphere is rolled over the molecule and produces a Richards-Connolly molecular surface (MS), which envelops the solvent-excluded volume of the molecule. In deep crevices, Connolly's method of calculating the MS has two deficiencies. First, it produces self-intersecting parts of the molecular surface, which must be removed to obtain the correct MS. Second, the correct MS is not smooth, i.e., the direction of the normal vector of the MS is not continuous, and some points of the MS are singular. We present an exact method for removing self-intersecting parts and smoothing the singular regions of the MS. The singular MS is smoothed by rolling a smoothing probe sphere over the inward side of the singular MS. The MS in the vicinity of singularities is replaced with the reentrant surface of the smoothing probe sphere. The smoothing method does not disturb the topology of a singular MS, and the smooth MS is a better approximation of the dielectric border between high dielectric solvent and the low dielectric molecular interior. The SIMS method generates a smooth molecular dot surface, which has a quasi-uniform dot distribution in two orthogonal directions on the molecular surface, which is invariant with molecular rotation and stable under changes in the molecular conformation, and which can be used in a variety of implicit methods of modeling solvent effects. The SIMS program is faster than the Connolly MS program, and in a matter of seconds generates a smooth dot MS of a 200-residue protein. The program is available from the authors on request (see http://femto.med.unc.edu/SIMS).