Protein structure prediction enhanced with evolutionary diversity: SPEED

Joe Debartolo, Glen Hocky, Michael Wilde, Jinbo Xu, Karl F. Freed, Tobin R. Sosnick

Research output: Contribution to journalArticlepeer-review


For naturally occurring proteins, similar sequence implies similar structure. Consequently, multiple sequence alignments (MSAs) often are used in template-based modeling of protein structure and have been incorporated into fragment-based assembly methods. Our previous homology-free structure prediction study introduced an algorithm that mimics the folding pathway by coupling the formation of secondary and tertiary structure. Moves in the Monte Carlo procedure involve only a change in a single pair of Φ,ψ backbone dihedral angles that are obtained from a Protein Data Bank-based distribution appropriate for each amino acid, conditional on the type and conformation of the flanking residues. We improve this method by using MSAs to enrich the sampling distribution, but in a manner that does not require structural knowledge of any protein sequence (i.e., not homologous fragment insertion). In combination with other tools, including clustering and refinement, the accuracies of the predicted secondary and tertiary structures are substantially improved and a global and position-resolved measure of confidence is introduced for the accuracy of the predictions. Performance of the method in the Critical Assessment of Structure Prediction (CASP8) is discussed. Published by Wiley-Blackwell.

Original languageEnglish (US)
Pages (from-to)520-534
Number of pages15
JournalProtein Science
Issue number3
StatePublished - Mar 2010


  • Folding pathway
  • ItFix
  • Monte Carlo simulated annealing
  • Multiple sequence alignment
  • Protein folding
  • Statistical potential

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology


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