On the use of different dielectric constants for computing individual and pairwise terms in poisson-boltzmann studies of protein ionization equilibrium

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Abstract

Poisson - Boltzmann (PB) models are a fast and common tool for studying electrostatic processes in proteins, particularly their ionization equilibrium (protonation and/or reduction), often yielding quite good results when compared with more detailed models. Yet, they are conceptually very simple and necessarily approximate, their empirical character being most evident when it comes to the choice of the dielectric constant assigned to the protein region. The present study analyzes several factors affecting the ability of PB-based methods to model protein ionization equilibrium. We give particular attention to a suggestion made by Warshel and co-workers (e.g., Sham et al. J. Phys. Chem. B 1997, 101, 4458) of using different protein dielectric constants for computing the individual (site) and the pairwise (site-site) terms of the ionization free energies. Our prediction of pKa values for several proteins indicates that no advantage is obtained by such a procedure, even for sites that are buried and/or display large pKa shifts relative to the solution values. In particular, the present methodology gives the best predictions using a dielectric constant around 20, for shifted/buried and nonshifted/exposed sites alike. The similarities and differences between the PB model and Warshel's PDLD/S model are discussed, as well as the reasons behind their apparently discrepant results. The present PB model is shown to predict also good reduction potentials in redox proteins.

Original languageEnglish
Pages (from-to)14691-14706
Number of pages16
JournalJournal of Physical Chemistry B
Volume109
Issue number30
DOIs
Publication statusPublished - 4 Aug 2005

Keywords

  • Phase equilibria
  • Poisson equation
  • Electrostatics
  • Ionization
  • Permittivity
  • pH effects

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