Electrostatics-defying interaction between arginine termini as a thermodynamic driving force in protein-protein interaction

• Published in: Proteins, structure, function, and bioinformatics structure, function, and bioinformatics, 2009-01, Vol.74 (1), p.155-163
• Main Authors: Pednekar, Deepa, Tendulkar, Abhijit, Durani, Susheel
• Format: Article
• Language: English
• Subjects: Arginine - chemistry; Arginine - metabolism; arginine-arginine interaction; cation-π bond; Computer Simulation; Guanidine - chemistry; Guanidine - metabolism; hotspots; Hydrogen Bonding; Ligands; Models, Molecular; molecular recognition; polarization effect; Protein Folding; Protein Multimerization; protein-protein interaction; Proteins - chemistry; Proteins - metabolism; Quantum Theory; Solvents - chemistry; Static Electricity; Thermodynamics
• ISSN: 0887-3585; 1097-0134
• DOI: 10.1002/prot.22142

Apparent electrostatics‐defying clustering of arginines attributed as screening effect of solvent is in this study examined as a possible thermodynamic driving force in protein–protein interaction. A dataset of 266 protein dimers is found to have ∼22% arginines mutually paired and ∼17% pairs in interaction across interfaces and thus putative “hotspots” of protein–protein interaction. The pairing, uncorrelated with inter or intramolecular context, could be contributing in protein folding as well, and, uncorrelated with solvent access, could be driven by effects that are generic to solvent and protein structures. Mutually stacked at shorter distances but in diverse geometrical modes otherwise, the cations tend to be in gross deficit of hydrogen‐bond partners, and contributing electrostatics across protein–protein interface that, on average, is repulsive for protein–protein interaction. Embedded in local environment enriched in polarizable residues, aromatic, aliphatic, and anionic, the arginines may contribute to protein–protein interaction via environmental polarization response to electrostatics of cation clustering, a possible new principle in molecular recognition. Proteins 2009. © 2008 Wiley‐Liss, Inc.