BIOPHYSICAL THEORY AND MODELING |
Poisson-Boltzmann calculations of non-specific salt effects on protein-protein binding free energies
Claudia Bertonati 1, Barry Honig 1 and Emil Alexov 1*
1 Howard Hughes Medical Institute
* To whom correspondence should be addressed. E-mail: ealexov{at}clemson.edu.
Submitted on June 26, 2006
Revised on July 23, 2006
Accepted on 5 December 2006
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Abstract |
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The salt dependence of the binding free energy of five protein-protein hetero-dimers and two homo-dimers/tetramers was calculated from numerical solutions to the Poisson-Boltzmann equation. Overall, the agreement with experimental values is very good. In all cases except one involving the highly charged lactoglobulin homo-dimer, increasing the salt concentration is found both experimentally and theoretically to decrease the binding affinity. In order to clarify the source of salt effects, the salt-dependent free energy of binding is partitioned into screening terms and to self energy terms which involve the interaction of the charge distribution of a monomer with its own ion atmosphere. In six of the seven complexes studied screening makes the largest contribution but self energy effects can also be significant. The calculated salt effects are found to be insensitive to force field parameters and to the internal dielectric constant assigned to the monomers. Non-linearities due to high charge densities, which are extremely important in the binding of proteins to negatively charged membrane surfaces and to nucleic acids, make much smaller contributions to the protein-protein complexes studied here, with exception of highly charged lactoglobulin dimer. Our results indicate that the Poisson-Boltzmann equation captures much of the physical basis of the non-specific salt dependence of protein-protein complexation.
Key Words:
Poisson-Boltzmann equation, binding free energy, electrostatics, protein-protein interactions, salt dependence
