Free Energy of Solvated Salt Bridges: A Simulation and Experimental Study

Charged amino acids are the most common on surfaces of proteins and understanding the interactions between these charged amino acids, salt bridging, is crucial for understanding protein–protein interactions. Previous simulations have been limited to implicit solvent or fixed binding geometry due to...

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Bibliographic Details
Published in:The journal of physical chemistry. B 2013-06, Vol.117 (24), p.7254-7259
Main Authors: White, Andrew D, Keefe, Andrew J, Ella-Menye, Jean-Rene, Nowinski, Ann K, Shao, Qing, Pfaendtner, Jim, Jiang, Shaoyi
Format: Article
Language:English
Subjects:
Amino acids
Amino Acids - chemistry
Biological and medical sciences
Bridges (structures)
Bridging
Charging
Free energy
Fundamental and applied biological sciences. Psychology
Hydration
Miscellaneous
Models, Molecular
Molecular biophysics
Molecular Dynamics Simulation
Molecular Structure
Nuclear Magnetic Resonance, Biomolecular
Orientation
Physical chemistry in biology
Proteins - chemistry
Salts - chemistry
Simulation
Solubility
Solvents - chemistry
Surface Properties
Water - chemistry
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Summary:Charged amino acids are the most common on surfaces of proteins and understanding the interactions between these charged amino acids, salt bridging, is crucial for understanding protein–protein interactions. Previous simulations have been limited to implicit solvent or fixed binding geometry due to the sampling required for converged free energies. Using well-tempered metadynamics, we have calculated salt bridge free energy surfaces in water and confirmed the results with NMR experiments. The simulations give binding free energies, quantitative ranking of salt bridging strength, and insights into the hydration of the salt bridges. The arginine–aspartate salt bridge was found to be the weakest and arginine-glutamate the strongest, showing that arginine can discriminate between aspartate and glutamate, whereas the salt bridges with lysine are indistinguishable in their free energy. The salt bridging hydration is found to be complementary to salt bridge orientation with arginine having specific orientations.
ISSN:1520-6106
1520-5207
DOI:10.1021/jp4024469