Bounding the electrostatic free energies associated with linear continuummodels of molecular solvation

摘要

The importance of electrostatic interactions in molecular biology has driven extensive researchtoward the development of accurate and efficient theoretical and computational models. Linearcontinuum electrostatic theory has been surprisingly successful, but the computational costsassociated with solving the associated partial differential equations (PDEs) preclude the theory's usein most dynamical simulations. Modern generalized-Born models for electrostatics can reproducePDE-based calculations to within a few percent and are extremely computationally efficient but donot always faithfully reproduce interactions between chemical groups. Recent work has shown thata boundary-integral-equation formulation of the PDE problem leads naturally to a new approachcalled boundary-integral-based electrostatics estimation (BIBEE) to approximate electrostaticinteractions. In the present paper, we prove that the BIBEE method can be used to rigorously boundthe actual continuum-theory electrostatic free energy. The bounds are validated using a set of morethan 600 proteins. Detailed numerical results are presented for structures of the peptidemet-enkephalin taken from a molecular-dynamics simulation. These bounds, in combination withour demonstration that the BIBEE methods accurately reproduce pairwise interactions, suggest anew approach toward building a highly accurate yet computationally tractable electrostaticmodel.