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

DeBartolo J,Colubri A,Jha AK,Fitzgerald JE,Freed KF,Sosnick TR

doi

10.1073/pnas.0811363106

subject

Has Abstract

pub_date

2009-03-10 00:00:00

pages

3734-9

issue

10

eissn

0027-8424

issn

1091-6490

pii

0811363106

journal_volume

106

pub_type

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