BIOPHYSICAL THEORY AND MODELING |
Optimization of electrostatic interactions in protein-protein complexes
Kelly Brock 1, Kemper Talley 1, Kacey Coley 1, Petras Kundrotas 2 and Emil Alexov 2*
1 South Carolina Governor School for Science and Mathematics
2 Clemson University
* To whom correspondence should be addressed. E-mail: ealexov{at}clemson.edu.
Submitted on May 8, 2007
Revised on June 4, 2007
Accepted on 25 June 2007
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Abstract |
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In this paper we present a statistical analysis of the electrostatic properties of 298 protein-protein complexes and 360 domain-domain structures extracted from the previously developed database of protein complexes (ProtCom, http://www.ces.clemson.edu/compbio/protcom). For each structure in the dataset we calculated the total electrostatic energy of the binding and its two components, Coulombic and reaction field energy. It was found that in a vast majority of the cases (more than 90 %), the total electrostatic component of the binding energy was unfavorable. At the same time, the Coulombic component of the binding energy was found to favor the complex formation while the reaction field component of the binding energy opposed the binding. It was also demonstrated that the components in a wild-type (WT) structure are optimized/anti-optimized with respect to the corresponding distributions, arising from random shuffling of the charged side chains. The degree of this optimization was assessed through the Z-score of WT energy in respect to the random distribution. It was found that the Z-scores of Coulombic interactions peek at a considerably negative value for all 658 cases considered while the Z-score of the reaction field energy varied among different types of complexes. All these findings indicate that the Coulombic interactions within WT protein-protein complexes are optimized in order to favor the complex formation while the total electrostatic energy predominantly opposes the binding. This observation was used to discriminate WT structures among sets of structural decoys and showed that the electrostatic component of the binding energy is not a good discriminator of the WT, while Coulombic or reaction field energies perform better depending of the decoy set used.
Key Words:
Binding energy, Decoy ranking, Electrostatics, Poisson-Boltzmann equation, Protein-protein complexes
