SIMS: computation of a smooth invariant molecular surface

Area of Science:

• Computational chemistry
• Molecular modeling
• Biophysics

Background:

• Traditional molecular surface calculations, like Connolly's method, produce surfaces with self-intersections and singularities.
• These deficiencies in molecular surface (MS) calculations hinder accurate modeling of solvent effects.
• Existing methods require complex post-processing to correct for self-intersections and non-smoothness.

Purpose of the Study:

• To introduce the Smooth Invariant Molecular Surface (SIMS) method for calculating molecular surfaces.
• To address the limitations of existing methods by providing an exact and efficient way to generate smooth molecular surfaces.
• To improve the approximation of the dielectric boundary between solvent and molecular interior.

Main Methods:

• The SIMS method utilizes two probe spheres: one for generating the initial molecular surface (MS) and another for smoothing.
• A solvent probe sphere rolls over the molecule to create an initial MS, enveloping the solvent-excluded volume.
• A smoothing probe sphere is rolled on the inward side of singular regions to replace reentrant surfaces, ensuring smoothness without altering topology.

Main Results:

• SIMS accurately removes self-intersecting parts and smooths singular regions of the molecular surface.
• The generated SIMS surface exhibits a quasi-uniform dot distribution, invariant to molecular rotation and stable under conformational changes.
• The SIMS program is significantly faster than the Connolly MS program, processing a 200-residue protein in seconds.

Conclusions:

• The SIMS method provides a superior, smooth molecular surface representation compared to previous methods.
• The smooth MS generated by SIMS offers a better approximation of the dielectric boundary, crucial for implicit solvent modeling.
• SIMS is an efficient and robust computational tool for molecular surface generation in various implicit solvent modeling applications.