title: Designability, aggregation propensity and duplication of disease-associated proteins.
abstract: Over 2000 proteins in the Ensembl human genome database have been linked with disease information from OMIM. In comparison with all human proteins, we find that disease-associated proteins tend to have less designable folds in terms of their SCOP family counts, suggesting that they are intrinsically less robust to mutation and environmental stress. Disease proteins also tend to have isoelectric points closer to neutrality and more alternating hydrophilic-hydrophobic amino acid stretches compared with the average human protein. These results suggest that protein aggregation is a significant phenomenon associated with diseases. Another finding in this work is that many disease proteins are highly sequence similar to other disease proteins, suggesting that gene duplication has contributed to the expansion of disease-prone protein families.
authors.affiliation: Institute for Bioinformatics, GSF, National Research Center for Environment and Health, Ingolstädter Landstrasse 1, D-85764 Neuherberg, Germany.
authors.forename: Philip
authors.initials: P
authors.lastname: Wong
authors.forename: Andreas
authors.initials: A
authors.lastname: Fritz
authors.forename: Dmitrij
authors.initials: D
authors.lastname: Frishman
mesh_terms: D019943:Amino Acid Substitution; D030541:Databases, Genetic; D004194:Disease; D015195:Drug Design; D020440:Gene Duplication; D015894:Genome, Human; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007526:Isoelectric Point; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics*
chemical_list: D011506:Proteins