TY - JOUR
T1 - Free energy of solvated salt bridges
T2 - A simulation and experimental study
AU - White, Andrew D.
AU - Keefe, Andrew J.
AU - Ella-Menye, Jean Rene
AU - Nowinski, Ann K.
AU - Shao, Qing
AU - Pfaendtner, Jim
AU - Jiang, Shaoyi
PY - 2013/6/20
Y1 - 2013/6/20
N2 - 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.
AB - 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.
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U2 - 10.1021/jp4024469
DO - 10.1021/jp4024469
M3 - Article
C2 - 23697872
AN - SCOPUS:84879408451
SN - 1520-6106
VL - 117
SP - 7254
EP - 7259
JO - Journal of Physical Chemistry B
JF - Journal of Physical Chemistry B
IS - 24
ER -