Protein Structure and Function: Application of Bioinformatics Methods - John Rigden 2014

Bioinformatics Methods for Studying the Structure and Function of Disordered Proteins
Functional Classification of IDPs
Functional Classification of IDPs Based on Gene Ontology

A number of studies have addressed the prevalence of disordered structures in certain functional protein classes (Iakoucheva et al. 2002; Ward et al. 2004; Tompa et al. 2006; Xie et al. 2007). Typically, these studies rely on the Gene Ontology (GO) framework (Ashbumer et al. 2000), examining protein disorder across all three ontological domains: molecular Functions, biological processes, and cellular components. Researchers consistently arrive at similar Conclusions: disorder is significantly more prevalent in eukaryotes than in prokaryotes, and it is a common feature of Proteins involved in regulatory and signaling pathways. From the perspective of molecular function, the highest levels of disorder are found in categories such as METABOLISM/31.html">Transcription regulation, protein Kinases, transcription factors, and DNA binding, whereas oxidoreductase, catalytic, ligase, and structural molecule categories exhibit low levels. In terms of biological processes, high levels of disorder characterize development, protein phosphorylation, Transcriptional Regulation, and signal Transduction, whereas disorder is rare in Biosynthesis and energy pathways. Regarding cellular localization, disorder predominates in nuclear, chromosomal, and cytoskeletal proteins, while mitochondrial, cytoplasmic, and Membrane Proteins are characterized by low levels of disorder.

Similar patterns have been observed when predictions were applied to extensive disordered regions widely considered to be functionally significant (Xie et al. 2007). An analysis of biological process keywords from the SwissProt database revealed a strong correlation with structural disorder—both positive (e.g., for differentiation, transcription, and transcriptional regulation) and negative (e.g., for biosynthesis, transport, electron transport, and Glycolysis) (Xie et al. 2007). When analyzing molecular function keywords, the strongest positive correlation was observed for ribonucleoproteins, ribosomal proteins, and developmental proteins, whereas oxidoreductases, transferases, lyases, and Hydrolases exhibited a negative correlation. Out of 710 function-describing keywords in the SwissProt database, 238 showed a pronounced positive correlation and 302 a pronounced negative correlation with structural disorder, while 170 keywords remained unclassified.

All studies addressing this issue share a common premise: proteins with regulatory functions exhibit a positive correlation with structural disorder, whereas proteins with catalytic functions are characterized by a negative relationship with disorder.