Increasing Protein Stability by Polar Surface Residues: Domain-Wide Consequences of Interactions Within a Loop

We have examined the influence of surface hydrogen bonds on the stability of proteins by studying the effects of mutations of human immunoglobulin light chain variable domain (VL). In addition to the variants Y27dD, N28F, and T94H of protein κIV Len that were previously described, we characterized mutants M4L, L27cN, L27cQ, and K39T, double mutant M4L/Y27dD, and triple mutant M4L/Y27dD/T94H. The triple mutant had an enhanced thermodynamic...