Protein structure prediction enhanced with evolutionary diversity : SPEED.

Journal Article · Mon Mar 01 04:00:00 EST 2010 · Protein Sci.

DOI:https://doi.org/10.1002/pro.330· OSTI ID:975474

DeBartolo, J; Hocky, G; Wilde, M; Xu, J; Freed, K F; Sosnick, T R

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 {phi},{psi} 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.

• Research Organization: Argonne National Laboratory (ANL)
• Sponsoring Organization: SC; NSF; NIH; Toyota Technological Inst.
• DOE Contract Number: AC02-06CH11357
• OSTI ID: 975474
• Report Number(s): ANL/MCS/JA-65868
• Journal Information: Protein Sci., Journal Name: Protein Sci. Journal Issue: 3 ; Mar. 2010 Vol. 19
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ACCURACY
ALGORITHMS
AMINO ACIDS
DISTRIBUTION
FORECASTING
PERFORMANCE
PROTEIN STRUCTURE
PROTEINS
RESIDUES
SAMPLING
SIMULATION
VELOCITY