Unit

UNIT 8.11 Structure-Based pKa Calculations Using Continuum Electrostatics Methods

  1. Carolyn A. Fitch,
  2. Bertrand García-Moreno E.

Published Online: 1 JAN 2007

DOI: 10.1002/0471250953.bi0811s16

Current Protocols in Bioinformatics

Current Protocols in Bioinformatics

How to Cite

Fitch, C. A. and García-Moreno E., B. 2007. Structure-Based pKa Calculations Using Continuum Electrostatics Methods. Current Protocols in Bioinformatics. 16:8.11:8.11.1–8.11.22.

Author Information

  1. Johns Hopkins University, Baltimore, Maryland

Publication History

  1. Published Online: 1 JAN 2007
  2. Published Print: DEC 2006

Abstract

Electrostatic free energy is useful for correlating structure with function in proteins in which ionizable groups play essential functional roles. To this end, the pKa values of ionizable groups must be known and their molecular determinants must be understood. Structure-based calculations of electrostatic energies and pKa values are necessary for this purpose. This unit describes protocols for pKa calculations with continuum electrostatics methods based on the numerical solution of the linearized Poisson-Boltzmann equation by the method of finite differences. Critical discussion of key parameters, approximations, and shortcomings of these methods is included. Two protocols are described for calculations with methods modified empirically to maximize agreement between measured and calculated pKa values. Applied judiciously, these methods can contribute useful and novel insight into properties of surface ionizable groups in proteins.

Keywords:

  • pKa calculations;
  • continuum electrostatics;
  • finite difference;
  • Poisson-Boltzmann;
  • UBHD