title: Interpreting the Coulomb-field approximation for generalized-Born electrostatics using boundary-integral equation theory.
abstract: The importance of molecular electrostatic interactions in aqueous solution has motivated extensive research into physical models and numerical methods for their estimation. The computational costs associated with simulations that include many explicit water molecules have driven the development of implicit-solvent models, with generalized-Born (GB) models among the most popular of these. In this paper, we analyze a boundary-integral equation interpretation for the Coulomb-field approximation (CFA), which plays a central role in most GB models. This interpretation offers new insights into the nature of the CFA, which traditionally has been assessed using only a single point charge in the solute. The boundary-integral interpretation of the CFA allows the use of multiple point charges, or even continuous charge distributions, leading naturally to methods that eliminate the interpolation inaccuracies associated with the Still equation. This approach, which we call boundary-integral-based electrostatic estimation by the CFA (BIBEE/CFA), is most accurate when the molecular charge distribution generates a smooth normal displacement field at the solute-solvent boundary, and CFA-based GB methods perform similarly. Conversely, both methods are least accurate for charge distributions that give rise to rapidly varying or highly localized normal displacement fields. Supporting this analysis are comparisons of the reaction-potential matrices calculated using GB methods and boundary-element-method (BEM) simulations. An approximation similar to BIBEE/CFA exhibits complementary behavior, with superior accuracy for charge distributions that generate rapidly varying normal fields and poorer accuracy for distributions that produce smooth fields. This approximation, BIBEE by preconditioning (BIBEE/P), essentially generates initial guesses for preconditioned Krylov-subspace iterative BEMs. Thus, iterative refinement of the BIBEE/P results recovers the BEM solution; excellent agreement is obtained in only a few iterations. The boundary-integral-equation framework may also provide a means to derive rigorous results explaining how the empirical correction terms in many modern GB models significantly improve accuracy despite their simple analytical forms.
authors.affiliation: Mathematics and Computer Science Division, Argonne National Laboratory, Argonne, Illinois 60439, USA. jbardhan@alum.mit.edu
authors.forename: Jaydeep P
authors.initials: JP
authors.lastname: Bardhan
mesh_terms: D003201:Computers; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000737:chemistry; D008956:Models, Chemical; D009842:Oligopeptides / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D055672:Static Electricity; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D009842:Oligopeptides; D012997:Solvents; D014867:Water; D051357:Cyclin-Dependent Kinase 2