MoRFpred, a computational tool for sequence-based prediction and characterization of short disorder-to-order transitioning binding regions in proteins

  • Disfani F
  • Hsu W
  • Mizianty M
 et al. 
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Abstract

MOTIVATION: Molecular recognition features (MoRFs) are short binding regions located within longer intrinsically disordered regions that bind to protein partners via disorder-to-order transitions. MoRFs are implicated in important processes including signaling and regulation. However, only a limited number of experimentally validated MoRFs is known, which motivates development of computational methods that predict MoRFs from protein chains.

RESULTS: We introduce a new MoRF predictor, MoRFpred, which identifies all MoRF types (α, β, coil and complex). We develop a comprehensive dataset of annotated MoRFs to build and empirically compare our method. MoRFpred utilizes a novel design in which annotations generated by sequence alignment are fused with predictions generated by a Support Vector Machine (SVM), which uses a custom designed set of sequence-derived features. The features provide information about evolutionary profiles, selected physiochemical properties of amino acids, and predicted disorder, solvent accessibility and B-factors. Empirical evaluation on several datasets shows that MoRFpred outperforms related methods: α-MoRF-Pred that predicts α-MoRFs and ANCHOR which finds disordered regions that become ordered when bound to a globular partner. We show that our predicted (new) MoRF regions have non-random sequence similarity with native MoRFs. We use this observation along with the fact that predictions with higher probability are more accurate to identify putative MoRF regions. We also identify a few sequence-derived hallmarks of MoRFs. They are characterized by dips in the disorder predictions and higher hydrophobicity and stability when compared to adjacent (in the chain) residues.

AVAILABILITY: http://biomine.ece.ualberta.ca/MoRFpred/; http://biomine.ece.ualberta.ca/MoRFpred/Supplement.pdf.

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