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Phosphorylated Sites on the Disordered Interface Signatures the Interacting Behavior of Proteins - A Comparative Mapping of Phosphorylation Propensities on Disordered Interfaces of Interactome and Negatome
1 , 1 , 1 , 1 , 1 , * 2, 3
1  Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Hyderabad – 500 016, India.
2  In silico Research Laboratory, Eminent Biosciences, 91, Sector-A, Mahalakshmi Nagar, Indore - 452010, Madhya Pradesh, India.
3  Bioinformatics Research Laboratory, LeGene Biosciences Pvt. Ltd. Indore - 452010, Mahdya Pradesh , India.


Hub proteins in interaction networks involved in signaling pathways are known to have more disordered residues than non-hubs. Since the signaling mechanisms involving PPI are regulated by phosphorylation, disordered interfaces could be thought to be extremely phosphorylated. In the present study we sought to map the phosphorylated sites onto disordered regions on interacting proteins-Interactomes and non-interacting proteins-Negatomes. Dataset of non-interacting protein included 784 proteins retrieved from Negatome database 2.0. 2252 interacting proteins were retrieved from “GeneMania”. Intrinsically disordered regions were predicted with “Disopred” program. The binding interfaces were defined by “PDBePISA” server, while, phosphorylation sites were derived from “NetPhos” program. All phosphorylation sites were mapped onto protein structures using alignments calculated by the MUSCLE program. As anticipated, the extent of phosphorylation in interactomes were significantly higher in disordered regions to its ordered counter parts (p=0.04). Insights revealed that the disordered regions in negatome were sparse in comparison to those in interactomes (p<0.0024). Declined phosphorylated sites were observed in negatomes. The widespread non-flexible and ordered regions in the negatomes confer the non interacting nature of the protein in turn makes it poor participant in signal transduction that involves phosphorylation. Our study sheds light on the importance of phosphorylated sites on disordered regions as a mark to decide whether protein would possibly interact or not.

Keywords: Disordered regions, Phosphorylation sites, Interactomes, Negatomes
Comments on this paper
Humbert G. Díaz
Dear authors,

Thank you by this contribution to Mol2Net conference!
I found both the concept and conclusions very interesting, indeed.

Could be incorporated other aspects like hydrophobic/polar regions, or carry out a
cross study with RNA/DNA accounting for other aspects like hydrogen bonding/free, encoding/non-encoding regions etc.?

Could be used the probability of errors of individuals methods reported by their respective authors or something?
Perhaps some estimation in the line p(overall-error) = p(binding-error) *p(disorder-error)*p(phosphorylation-error)^2 ?

Once again, thank you by submitting this very interesting contribution and by your support to mol2net!!!
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