Document Type
Article
Publication Date
2013
Keywords
Cluster, PONDR, Intrinsically, Disordered, Kidera, Unfolded, Pfam, Protein, Cancer, Diabetes, Phylogenetic, Mammals, Eukaryota, Viruses, Bacteria, Archaea, APOC1, ANFB, DBND1, BAALC, PPR1A, ATTY, DSS1, TR13C, MYBB, LZTS2, HNF1A, NFM, APC, BRCA2
Digital Object Identifier (DOI)
https://doi.org/10.4161%2Fidp.25724
Abstract
The Pfam database groups regions of proteins by how well hidden Markov models (HMMs) can be trained to recognize similarities among them. Conservation pressure is probably in play here. The Pfam seed training set includes sequence and structure information, being drawn largely from the PDB. A long standing hypothesis among intrinsically disordered protein (IDP) investigators has held that conservation pressures are also at play in the evolution of different kinds of intrinsic disorder, but we find that predicted intrinsic disorder (PID) is not always conserved across Pfam domains. Here we analyze distributions and clusters of PID regions in 193024 members of the version 23.0 Pfam seed database. To include the maximum information available for proteins that remain unfolded in solution, we employ the 10 linearly independent Kidera factors1–3 for the amino acids, combined with PONDR4 predictions of disorder tendency, to transform the sequences of these Pfam members into an 11 column matrix where the number of rows is the length of each Pfam region. Cluster analyses of the set of all regions, including those that are folded, show 6 groupings of domains. Cluster analyses of domains with mean VSL2b scores greater than 0.5 (half predicted disorder or more) show at least 3 separated groups. It is hypothesized that grouping sets into shorter sequences with more uniform length will reveal more information about intrinsic disorder and lead to more finely structured and perhaps more accurate predictions. HMMs could be trained to include this information.
Rights Information
This work is licensed under a Creative Commons Attribution-Noncommercial 3.0 License
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Intrinsically Disordered Proteins, v. 1, issue 1, art. e25724
Scholar Commons Citation
Williams, Robert W.; Xue, Bin; Uversky, Vladimir N.; and Dunker, A. Keith, "Distribution and Cluster Analysis of Predicted Intrinsically Disordered Protein Pfam Domains" (2013). Molecular Medicine Faculty Publications. 449.
https://digitalcommons.usf.edu/mme_facpub/449
