title: Mimicking the folding pathway to improve homology-free protein structure prediction.
abstract: Since the demonstration that the sequence of a protein encodes its structure, the prediction of structure from sequence remains an outstanding problem that impacts numerous scientific disciplines, including many genome projects. By iteratively fixing secondary structure assignments of residues during Monte Carlo simulations of folding, our coarse-grained model without information concerning homology or explicit side chains can outperform current homology-based secondary structure prediction methods for many proteins. The computationally rapid algorithm using only single (phi,psi) dihedral angle moves also generates tertiary structures of accuracy comparable with existing all-atom methods for many small proteins, particularly those with low homology. Hence, given appropriate search strategies and scoring functions, reduced representations can be used for accurately predicting secondary structure and providing 3D structures, thereby increasing the size of proteins approachable by homology-free methods and the accuracy of template methods that depend on a high-quality input secondary structure.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Joe
authors.initials: J
authors.lastname: DeBartolo
authors.forename: Andrés
authors.initials: A
authors.lastname: Colubri
authors.forename: Abhishek K
authors.initials: AK
authors.lastname: Jha
authors.forename: James E
authors.initials: JE
authors.lastname: Fitzgerald
authors.forename: Karl F
authors.initials: KF
authors.lastname: Freed
authors.forename: Tobin R
authors.initials: TR
authors.lastname: Sosnick
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D040681:Structural Homology, Protein
chemical_list: D011506:Proteins