Free energy of solvated salt bridges: A simulation and experimental study

Andrew D. White, Andrew J. Keefe, Jean Rene Ella-Menye, Ann K. Nowinski, Qing Shao, Jim Pfaendtner, Shaoyi Jiang

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


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.

Original languageEnglish
Pages (from-to)7254-7259
Number of pages6
JournalJournal of Physical Chemistry B
Issue number24
StatePublished - Jun 20 2013

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry


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