Analysis of Protein Disorder Predictions in the Light of a Protein Structural Alphabet.

Biomolecules
Alexandre G de Brevern

Abstract

Intrinsically-disordered protein (IDP) characterization was an amazing change of paradigm in our classical sequence-structure-function theory. Moreover, IDPs are over-represented in major disease pathways and are now often targeted using small molecules for therapeutic purposes. This has had created a complex continuum from order-that encompasses rigid and flexible regions-to disorder regions; the latter being not accessible through classical crystallographic methodologies. In X-ray structures, the notion of order is dictated by access to resolved atom positions, providing rigidity and flexibility information with low and high experimental B-factors, while disorder is associated with the missing (non-resolved) residues. Nonetheless, some rigid regions can be found in disorder regions. Using ensembles of IDPs, their local conformations were analyzed in the light of a structural alphabet. An entropy index derived from this structural alphabet allowed us to propose a continuum of states from rigidity to flexibility and finally disorder. In this study, the analysis was extended to comparing these results to disorder predictions, underlying a limited correlation, and so opening new ideas to characterize and predict disorder.

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Citations

Sep 19, 2020·Biochimie·Alexandre G de Brevern

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Methods Mentioned

BETA
X-ray
electron microscopy
NMR

Software Mentioned

R
IUPred2A
DISOselect
OPAL
Basic Local Alignment Search Tool ( PSI - BLAST )
PBxplore
DECIPHER
PreSMos
PrDOS
Disopred3

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