Accuracy of continuum electrostatic calculations based on three common dielectric boundary definitions

Area of Science:

• Computational Chemistry
• Molecular Modeling
• Physical Chemistry

Background:

• Accurate calculation of electrostatic solvation energy (ΔG_el) is crucial for understanding molecular interactions in solution.
• Implicit solvation models, such as Poisson-Boltzmann and Generalized Born, rely on defining a dielectric boundary (DB) between solute and solvent.
• The definition of this DB can influence the computed ΔG_el values.

Purpose of the Study:

• To investigate the impact of three common dielectric boundary (DB) definitions on the accuracy of electrostatic solvation energy (ΔG_el) calculations.
• To compare the performance of van der Waals (vdW), molecular surface (MS), and solvent accessible surface (SAS) DBs across different molecular structures.
• To determine the optimal probe radius for MS and SAS boundaries and assess their accuracy relative to explicit solvent calculations.

Main Methods:

• Calculated ΔG_el using Poisson-Boltzmann and Generalized Born models with different DB definitions (vdW, MS, SAS).
• Employed common atomic radii sets: BONDI, PARSE, and ZAP9.
• Used explicit solvent ΔG_el values as the reference for accuracy assessment.

Main Results:

• Van der Waals (vdW) DB definitions result in larger errors in ΔG_el compared to molecular surface (MS) DBs for common atomic radii.
• The optimal probe radius for MS DB varies by structure type; SAS DB becomes optimal around 0.2 Å, yielding comparable accuracy to MS.
• For small molecules, optimal vdW DBs can be as accurate as optimal MS DBs, with virtually equivalent pairwise interactions. However, for larger molecules like small proteins, significant differences in pairwise interactions arise between optimal vdW and MS DBs, even when total ΔG_el is similar.

Conclusions:

• The molecular surface (MS) dielectric boundary definition is generally more physically realistic for electrostatic solvation energy calculations, particularly for larger molecules.
• While optimal vdW DBs can be accurate for small molecules, the choice of DB definition becomes critical for larger systems where pairwise interactions can diverge.
• Further research may be needed to refine DB definitions for diverse molecular systems and improve the accuracy of implicit solvation models.