This article is part of the supplement: Selected articles from the Computational Structural Bioinformatics Workshop 2009
Discrimination of thermophilic and mesophilic proteins
1 National Cancer Institute, Laboratory of Molecular Biology, 37 Convent Dr., MS 4264, Bethesda, MD 20892, USA
2 Department of Bioinformatics and Computational Biology, George Mason University, 10900 University Blvd., Manassas VA 20110, USA
BMC Structural Biology 2010, 10(Suppl 1):S5 doi:10.1186/1472-6807-10-S1-S5Published: 17 May 2010
There is a considerable literature on the source of the thermostability of proteins from thermophilic organisms. Understanding the mechanisms for this thermostability would provide insights into proteins generally and permit the design of synthetic hyperstable biocatalysts.
We have systematically tested a large number of sequence and structure derived quantities for their ability to discriminate thermostable proteins from their non-thermostable orthologs using sets of mesophile-thermophile ortholog pairs. Most of the quantities tested correspond to properties previously reported to be associated with thermostability. Many of the structure related properties were derived from the Delaunay tessellation of protein structures.
Carefully selected sequence based indices discriminate better than purely structure based indices. Combined sequence and structure based indices improve performance somewhat further. Based on our analysis, the strongest contributors to thermostability are an increase in ion pairs on the protein surface and a more strongly hydrophobic interior.