Strength of solvent-exposed salt-bridges

This paper uses a recently developed computer model to study the energetics of solvent-exposed salt-bridges. The model uses the "mining minima" method to compute conformational free energies with the CHARMm empirical force an d the generalized Born solvation model. Satisfactory agreement is obtained in comparison with the measured binding affinities of ion pairs in solution and with the salt-bridge energetics deduced from studies of salt-bridges i n helical peptides, The calculations suggest that stabilizing charge-charge interactions in helical peptides do not require well-defined salt-bridge c onformations. This is in agreement with crystallographic studies of charge pairs added to T4 lysozyme by site-directed mutagenesis. The computer model is also used to make a testable prediction that arginine and phosphotyrosi ne residues in an (i, i + 4) relationship will form a particularly strong s alt-bridge in helical peptides. The biological implications of these result s are discussed.