title: Free energy of solvated salt bridges: a simulation and experimental study.
abstract: 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.
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: White
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Keefe
authors.forename: Jean-Rene
authors.initials: JR
authors.lastname: Ella-Menye
authors.forename: Ann K
authors.initials: AK
authors.lastname: Nowinski
authors.forename: Qing
authors.initials: Q
authors.lastname: Shao
authors.forename: Jim
authors.initials: J
authors.lastname: Pfaendtner
authors.forename: Shaoyi
authors.initials: S
authors.lastname: Jiang
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011506:Proteins / Q000737:chemistry*; D012492:Salts / Q000737:chemistry; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013499:Surface Properties; D014867:Water / Q000737:chemistry
chemical_list: D000596:Amino Acids; D011506:Proteins; D012492:Salts; D012997:Solvents; D014867:Water