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Why Is There a Glass Ceiling for Threading Based Protein Structure Prediction Methods?

Jeffrey Skolnick1, Hongyi Zhou1

  • 1Center for the Study of Systems Biology, School of Biological Sciences, Georgia Institute of Technology , 950 Atlantic Drive Northwest, Atlanta, Georgia 30318, United States.

The Journal of Physical Chemistry. B
|October 18, 2016
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Summary
This summary is machine-generated.

Protein structure prediction via threading methods faces limitations due to inherent fold degeneracy. Current threading approaches have plateaued, necessitating novel protein structure prediction strategies.

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Area of Science:

  • Computational biology
  • Structural bioinformatics
  • Protein structure prediction

Background:

  • Threading approaches are widely used for predicting evolutionary distant protein structures.
  • These methods often succeed or fail on the same targets, irrespective of template availability.

Purpose of the Study:

  • To investigate the reasons behind the success or failure of protein threading.
  • To identify limitations in current protein structure prediction methodologies.

Main Methods:

  • Comparative analysis of threading approaches on various protein targets.
  • Utilized a novel contact map-based alignment algorithm.
  • Tested on artificial sequences selected for stability.

Main Results:

  • Protein structure threadability is intrinsically linked to the nature of the protein folds themselves.
  • Highly degenerate folds exhibit similar coarse-grained native contact alignments despite significant structural differences.
  • Non-threadable proteins demonstrate this fold degeneracy.

Conclusions:

  • Contemporary protein threading methods have reached their predictive limit.
  • New and innovative approaches are essential for advancing protein structure prediction.
  • Fold degeneracy is a key factor limiting the efficacy of current threading algorithms.