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In Silico Biology 7, 0023 (2007); ©2007, Bioinformation Systems e.V.  

Correlation between the structural stability and aggregation propensity of proteins

Susan Idicula-Thomas and Petety V. Balaji*

School of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400 076, India

* Corresponding author

Edited by E. Wingender; received December 18, 2006; revised February 08, 2007; accepted March 06, 2007; published April 11, 2007


Protein aggregation, being an outcome of improper protein folding, is largely dependent on the folding kinetics of a protein. Previous studies have reported a positive correlation between the stability of the secondary structural elements of a protein and their rate of folding/unfolding. In this in silico study, the secondary and tertiary structures of proteins a) that form inclusion bodies on overexpression in Escherichia coli, b) that form amyloid fibrils and c) that are soluble on overexpression in E. coli are analyzed for certain features that are known to be associated with structural stability. The study revealed that the soluble proteins seem to have a higher rate of folding (based on contact order) and a lower percentage of exposed hydrophobic residues as compared to the inclusion body forming or amyloidogenic proteins. The soluble proteins also seem to have a more favored helix and strand composition (based on the known secondary structural propensities the amino acids). The secondary structure analyses also reveal that the evolutionary pressure is directed against protein aggregation. This understanding of the positive correlation between structural stability and solubility, along with the other parameters known to influence aggregation, could be exploited in the design of mutations aimed at reducing the aggregation propensity of the proteins.

Keywords: amyloidogenicity, inclusion bodies, contact order, stability of secondary structures