title: Statistical significance of protein structure prediction by threading.
abstract: In this study, we estimate the statistical significance of structure prediction by threading. We introduce a single parameter epsilon that serves as a universal measure determining the probability that the best alignment is indeed a native-like analog. Parameter epsilon takes into account both length and composition of the query sequence and the number of decoys in threading simulation. It can be computed directly from the query sequence and potential of interactions, eliminating the need for sequence reshuffling and realignment. Although our theoretical analysis is general, here we compare its predictions with the results of gapless threading. Finally we estimate the number of decoys from which the native structure can be found by existing potentials of interactions. We discuss how this analysis can be extended to determine the optimal gap penalties for any sequence-structure alignment (threading) method, thus optimizing it to maximum possible performance.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Mirny
authors.forename: A V
authors.initials: AV
authors.lastname: Finkelstein
authors.forename: E I
authors.initials: EI
authors.lastname: Shakhnovich
mesh_terms: D015233:Models, Statistical; D008962:Models, Theoretical; D009010:Monte Carlo Method; D016011:Normal Distribution; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D011506:Proteins