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Accurate solution of multi‐region continuum biomolecule electrostatic problems using the linearized Poisson–Boltzmann equation with curved boundary elements
Author(s) -
Altman Michael D.,
Bardhan Jaydeep P.,
White Jacob K.,
Tidor Bruce
Publication year - 2008
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.21027
Subject(s) - boundary element method , solver , discretization , poisson–boltzmann equation , poisson's equation , generalized minimal residual method , boundary (topology) , boundary value problem , electrostatics , finite element method , mathematical analysis , physics , mathematics , linear system , mathematical optimization , quantum mechanics , ion , thermodynamics
Abstract We present a boundary‐element method (BEM) implementation for accurately solving problems in biomolecular electrostatics using the linearized Poisson–Boltzmann equation. Motivating this implementation is the desire to create a solver capable of precisely describing the geometries and topologies prevalent in continuum models of biological molecules. This implementation is enabled by the synthesis of four technologies developed or implemented specifically for this work. First, molecular and accessible surfaces used to describe dielectric and ion‐exclusion boundaries were discretized with curved boundary elements that faithfully reproduce molecular geometries. Second, we avoided explicitly forming the dense BEM matrices and instead solved the linear systems with a preconditioned iterative method (GMRES), using a matrix compression algorithm (FFTSVD) to accelerate matrix–vector multiplication. Third, robust numerical integration methods were employed to accurately evaluate singular and near‐singular integrals over the curved boundary elements. Fourth, we present a general boundary‐integral approach capable of modeling an arbitrary number of embedded homogeneous dielectric regions with differing dielectric constants, possible salt treatment, and point charges. A comparison of the presented BEM implementation and standard finite‐difference techniques demonstrates that for certain classes of electrostatic calculations, such as determining absolute electrostatic solvation and rigid‐binding free energies, the improved convergence properties of the BEM approach can have a significant impact on computed energetics. We also demonstrate that the improved accuracy offered by the curved‐element BEM is important when more sophisticated techniques, such as nonrigid‐binding models, are used to compute the relative electrostatic effects of molecular modifications. In addition, we show that electrostatic calculations requiring multiple solves using the same molecular geometry, such as charge optimization or component analysis, can be computed to high accuracy using the presented BEM approach, in compute times comparable to traditional finite‐difference methods. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009