Highly accurate sequence - based prediction of half - sphere exposures of amino acid residues in proteins

Abstract

Motivation: Solvent exposure of amino acid residues of proteins plays an important role in understanding and predicting protein structure, function and interactions. Solvent exposure can be characterized by several measures including solvent accessible surface area (ASA), residue depth (RD) and contact numbers (CN). More recently, an orientation-dependent contact number called half-sphere exposure (HSE) was introduced by separating the contacts within upper and down half spheres defined according to the Ca-Cb (HSEb) vector or neighboring Ca-Ca vectors (HSEa). HSEa calculated from protein structures was found to better describe the solvent exposure over ASA, CN and RD in many applications. Thus, a sequence-based prediction is desirable, as most proteins do not have experimentally determined structures. To our best knowledge, there is no method to predict HSEa and only one method to predict HSEb. Results: This study developed a novel method for predicting both HSEa and HSEb (SPIDER-HSE) that achieved a consistent performance for 10-fold cross validation and two independent tests. The correlation coefficients between predicted and measured HSEb (0.73 for upper sphere, 0.69 for down sphere and 0.76 for contact numbers) for the independent test set of 1199 proteins are significantly higher than existing methods. Moreover, predicted HSEa has a higher correlation coeffi- cient (0.46) to the stability change by residue mutants than predicted HSEb (0.37) and ASA (0.43). The results, together with its easy Ca-atom-based calculation, highlight the potential usefulness of predicted HSEa for protein structure prediction and refinement as well as function prediction