Quantitative Prediction of Critical Amino Acid Positions for Protein Folding

International audienceThe prediction of structural elements from the sequence is not only useful in determining the fold and function of proteins with unknown structure, but is also valuable in the design of protein engineering experiments, by locating critical regions of the polypeptide chain, with respect to folding and stability. Both thermodynamic and topological criteria have been used to define such amino acid sequence regions. The notion of folding nucleus comes from a thermodynamic view of folding, as the minimum set of amino acid residues necessary for the formation of a stable protein core [1]. The amino acids of the folding nucleus can be found experimentally by means of protein engineering studies [2]. However, it is difficult to perform this kind of experiments on a large scale. Therefore very limited data are actually available [3, 4, 5, 6]. An original topological analysis of available protein structures taken from the PDB [7], revealed a new property, common to almost all globular proteins: Closed Loops [8] or equivalently, TEFs (for Tightened-Ended-Fragments) [9, 10], are fragments with two basic properties: a) Their ends are located in the protein core and b) Their ends are close to each other in 3D space (