Entropy Drives the Formation of Salt Bridges in the Protein GB3

Abstract

Salt bridges are very common in proteins.But what drives the formation of protein salt bridges is not clear.Inthis work, we determined the strength of four salt bridges in the protein GB3 by measuring the DpK a values of the basic residues that constitute the salt bridges with ah ighly accurate NMR titration method at different temperatures.T he results show that the DpK a values increase with temperature,t hus indicating that the salt bridges are stronger at higher temperatures.Fitting of DpK a values to the vantHoff equation yields positive DHand DSvalues,thus indicating that entropydrives salt-bridge formation. Molecular dynamics simulations show that the protein and solvent make opposite contributions to DH and DS. Specifically,t he enthalpic gain contributed from the protein is more than offset by the enthalpic loss contributed from the solvent, whereas the entropic gain originates from the desolvation effect.