SALT BRIDGE INTERACTIONS - STABILITY OF THE IONIC AND NEUTRAL COMPLEXES IN THE GAS-PHASE, IN SOLUTION, AND IN PROTEINS

A theoretical study on the stability of the salt bridges in the gas ph ase, in solution, and in the interior of proteins is presented, The st udy is mainly focused on the interaction between acetate and methylgua nidinium ions, which were used as model compounds for the salt bridge between Asp (Glu) and Arg. Two different solvents (water and chlorofor m) were used to analyze the effect of varying the dielectric constant of the surrounding media on the salt bridge interaction. Calculations in protein environments were performed by using a set of selected prot ein crystal structures. In all cases attention was paid to the differe nce in stability between the ion pair and neutral hydrogen-bonded form s. Comparison of the results determined in the gas phase and in soluti on allows us to stress the large influence of the environment on the b inding process, as well as on the relative stability between the ionic and neutral complexes. The high anisotropy of proteins and the local microenvironment in the interior of proteins make a decisive contribut ion in modulating the energetics of the salt bridge. In general, the f ormation of salt bridges in proteins is not particularly favored, with the ion pair structure being preferred over the interaction between n eutral species. Proteins 32:67-79, 1998, (C) 1998 Wiley-Liss, Inc.