UNIT 8.11 Structure-Based pKa Calculations Using Continuum Electrostatics Methods
Published Online: 1 JAN 2007
Copyright © 2006 by John Wiley and Sons, Inc.
Lab Protocol Title
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.
- Published Online: 1 JAN 2007
- Published Print: DEC 2006
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.
- pKa calculations;
- continuum electrostatics;
- finite difference;