An amino acid has two sides: A new 2d measure provides a different view of solvent exposure

ABSTRACT The concept of amino acid solvent exposure is crucial for understanding and predict-ing various aspects of protein structure and func-tion. The traditional measures of solvent exposure however suffer from various shortcomings, like for example the inability to distinguish exposed, partly exposed, buried, and deeply buried residues. This article introduces a new measure of solvent expo-sure called Half-Sphere Exposure that addresses many of the shortcomings of other methods. The new measure outperforms other measures with re-spect to correlationwith protein stability, conserva-tion among fold homologs, amino acid-type depen-dency and interpretation. The measure consists of the number of C atoms in two half spheres around a residue’s C atom. Conceptually, one of the half spheres corresponds to the side chain’s neighbor-hood, the other half sphere being in the opposite direction. We show here that the two half spheres correspond to two regions around an amino acid that are surprisingly distinct in terms of geometry and energy. This aspect of protein structure intro-duced here forms the basis of the Half-Sphere Expo-sure measure. The results strongly suggest that in many respects, a 2D measure is inherently much better suited to describe solvent exposure than the traditional 1D measures. Importantly, Half-Sphere Exposure canbe calculated from theC atomcoordi-nates only, which abolishes the need for a full-atom model to calculate solvent exposure. Hence, the measure can be used in protein structure prediction methods that are based on various simplified mod-els. Half-Sphere Exposure has great potential for use in protein structure prediction and analysis. Proteins 2005;59:38–48. © 2005 Wiley-Liss, Inc. Key words: protein structure; coordination num-ber; residue depth; accessible solvent area; solvent exposure; simplifed mod-els; protein structure predictio