Computational Approaches for Inferring the Functions of Intrinsically Disordered Proteins

• Main Authors: Mihaly eVaradi, Wim eVranken, Mainak eGuharoy, Peter eTompa
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2015-08-01
• Series: Frontiers in Molecular Biosciences
• Subjects: intrinsically disordered proteins; Disorder prediction; IDP ensembles; IDP function; protein ensemble database
• Online Access: http://journal.frontiersin.org/Journal/10.3389/fmolb.2015.00045/full

Intrinsically disordered proteins (IDPs) are ubiquitously involved in cellular processes and often implicated in human pathological conditions. The critical biological roles of these proteins, despite not adopting a well-defined fold, encouraged structural biologists to revisit their views on the protein structure-function paradigm. Unfortunately, investigating the characteristics and describing the structural behavior of IDPs is far from trivial, and inferring the function(s) of a disordered protein region remains a major challenge. Computational methods have proven particularly relevant for studying IDPs: on the sequence level their dependence on distinct characteristics determined by the local amino acid context makes sequence-based prediction algorithms viable and reliable tools for large scale analyses, while on the structure level the in silico integration of fundamentally different experimental data types is essential to describe the behavior of a flexible protein chain. Here, we offer an overview of the latest developments and computational techniques that aim to uncover how protein function is connected to intrinsic disorder.