title: Long range Debye-Hückel correction for computation of grid-based electrostatic forces between biomacromolecules.
abstract: BACKGROUND
  Brownian dynamics (BD) simulations can be used to study very large molecular systems, such as models of the intracellular environment, using atomic-detail structures. Such simulations require strategies to contain the computational costs, especially for the computation of interaction forces and energies. A common approach is to compute interaction forces between macromolecules by precomputing their interaction potentials on three-dimensional discretized grids. For long-range interactions, such as electrostatics, grid-based methods are subject to finite size errors. We describe here the implementation of a Debye-Hückel correction to the grid-based electrostatic potential used in the SDA BD simulation software that was applied to simulate solutions of bovine serum albumin and of hen egg white lysozyme.
  
  
  RESULTS
  We found that the inclusion of the long-range electrostatic correction increased the accuracy of both the protein-protein interaction profiles and the protein diffusion coefficients at low ionic strength.
  
  
  CONCLUSIONS
  An advantage of this method is the low additional computational cost required to treat long-range electrostatic interactions in large biomacromolecular systems. Moreover, the implementation described here for BD simulations of protein solutions can also be applied in implicit solvent molecular dynamics simulations that make use of gridded interaction potentials.
authors.affiliation: Molecular and Cellular Modeling Group, Heidelberg Institute for Theoretical Studies (HITS), Schloß-Wolfsbrunnenweg 35, 69118 Heidelberg, Germany ; Center for Nanotechnology Innovation@NEST, Italian Institute of Technology, Piazza San Silvestro 12, Pisa, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Mereghetti
authors.affiliation: Molecular and Cellular Modeling Group, Heidelberg Institute for Theoretical Studies (HITS), Schloß-Wolfsbrunnenweg 35, 69118 Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Martinez
authors.affiliation: Molecular and Cellular Modeling Group, Heidelberg Institute for Theoretical Studies (HITS), Schloß-Wolfsbrunnenweg 35, 69118 Heidelberg, Germany ; Center for Molecular Biology (ZMBH), University of Heidelberg, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany.
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Wade
keywords: Brownian dynamics simulation; Continuum solvent electrostatics; Debye-Hückel; Discretization grid; Finite difference; Ionic strength; Poisson-Boltzmann equation; Protein diffusion; Second virial coefficient; Small angle scattering intensity