title: Systematic construction and prediction of the arrangement of the strands of sandwich proteins.
abstract: The problem of predicting the three-dimensional structure of a protein starting from its amino acid sequence is regarded as one of the most important open problems in biology. Here, we solve aspects of this problem for the so-called sandwich proteins that constitute a large class of proteins consisting of only beta-strands arranged in two sheets. A breakthrough for this class of proteins was announced in Kister et al. (Kister et al. 2002 Proc. Natl Acad. Sci. USA 99, 14 137-14 141), in which it was shown that sandwich proteins contain a certain invariant substructure called interlock. It was later noted that approximately 90% of the observed sandwich proteins are canonical, namely they are generated by certain geometrical structures. Here, employing a topological investigation, we prove that interlocks and geometrical structures are the direct consequence of certain biologically motivated fundamental principles. Furthermore, we construct all possible canonical motifs involving 6-10 strands. This construction limits dramatically the number of possible motifs. For example, for sandwich proteins with nine strands, the a priori number of possible canonical motifs exceeds 360000, whereas our construction yields only 49 geometrical structures and 625 canonical motifs.
authors.affiliation: Department of Computer Engineering and Informatics, University of Patras, 265 04 Patras, Greece. tsp@hpclab.ceid.upatras.gr
authors.forename: T S
authors.initials: TS
authors.lastname: Papatheodorou
authors.forename: A S
authors.initials: AS
authors.lastname: Fokas
mesh_terms: D020816:Amino Acid Motifs; D055592:Biophysical Phenomena; D008958:Models, Molecular; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*
chemical_list: D011506:Proteins