Lost hydrogen bonds and buried surface area: rationalising stability in globular proteins

Abstract

Of the many forces that contribute to the marginal stability of globular proteins, two particular interactions have been examined extensively over the last few decades. These are (i) the hydrophobic effect and its quantitative estimation through consideration of buried surface area, and (ii) hydrogen bonding in protein–water systems. In this paper, these interactions are calculated on the basis of geometrical considerations, and a high correlation is observed between the loss of potential hydrogen bonds (LHBs) and the buried surface area of apolar atoms, for all the proteins analysed in the protein databank. We show that this correlation, which we call the LHB model, can be applied to assess reliably the stability of X-ray structures, particularly at lower resolutions of 2.0–3.5 Å, local secondary structures and model structures of partly or misfolded proteins.