Confidence-guided local structure prediction with HHfrag

PLoS One. 2013 Oct 16;8(10):e76512. doi: 10.1371/journal.pone.0076512. eCollection 2013.

Abstract

We present a method to assess the reliability of local structure prediction from sequence. We introduce a greedy algorithm for filtering and enrichment of dynamic fragment libraries, compiled with remote-homology detection methods such as HHfrag. After filtering false hits at each target position, we reduce the fragment library to a minimal set of representative fragments, which are guaranteed to have correct local structure in regions of detectable conservation. We demonstrate that the location of conserved motifs in a protein sequence can be predicted by examining the recurrence and structural homogeneity of detected fragments. The resulting confidence score correlates with the local RMSD of the representative fragments and allows us to predict torsion angles from sequence with better accuracy compared to existing machine learning methods.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Proteins / chemistry*
  • Reproducibility of Results
  • Software*

Substances

  • Proteins

Grants and funding

This work has been supported by contract research “Methoden in den Lebenswissenschaften” of the Baden-Württemberg Stiftung, by Deutsche Forschungsgemeinschaft (DFG) grant HA 5918/1-1, and by the Max Planck Society. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.