PEDS Advance Access originally published online on September 9, 2005
Protein Engineering Design and Selection 2005 18(10):503-508; doi:10.1093/protein/gzi056
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Designability, aggregation propensity and duplication of disease-associated proteins
1Institute for Bioinformatics, GSF – National Research Center for Environment and Health, Ingolstädter Landstrasse 1, D-85764 Neuherberg, 2Biomax Informatics AG, Lochhamer Strasse 9, D-82152 Martinsried and 3Department of Genome Oriented Bioinformatics, Technische Universität München, Wissenschaftzentrum Weihenstephan, D-85350 Freising, Germany
4 To whom correspondence should be addressed at the Technische Universität München. E-mail: d.frishman{at}wzw.tum.de
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.
Keywords: aggregation/designability/disease/duplication
Received February 15, 2005; revised May 25, 2005; accepted August 3, 2005.
Edited by Luis Serrano