title: Folding RaCe: a robust method for predicting changes in protein folding rates upon point mutations.
abstract: BACKGROUND
  Protein engineering methods are commonly employed to decipher the folding mechanism of proteins and enzymes. However, such experiments are exceedingly time and resource intensive. It would therefore be advantageous to develop a simple computational tool to predict changes in folding rates upon mutations. Such a method should be able to rapidly provide the sequence position and chemical nature to modulate through mutation, to effect a particular change in rate. This can be of importance in protein folding, function or mechanistic studies.
  
  
  RESULTS
  We have developed a robust knowledge-based methodology to predict the changes in folding rates upon mutations formulated from amino and acid properties using multiple linear regression approach. We benchmarked this method against an experimental database of 790 point mutations from 26 two-state proteins. Mutants were first classified according to secondary structure, accessible surface area and position along the primary sequence. Three prime amino acid features eliciting the best relationship with folding rates change were then shortlisted for each class along with an optimized window length. We obtained a self-consistent mean absolute error of 0.36 s(-1) and a mean Pearson correlation coefficient (PCC) of 0.81. Jack-knife test resulted in a MAE of 0.42 s(-1) and a PCC of 0.73. Moreover, our method highlights the importance of outlier(s) detection and studying their implications in the folding mechanism.
  
  
  METHODS
  A web server 'Folding RaCe' has been developed and is available at http://www.iitm.ac.in/bioinfo/proteinfolding/foldingrace.html.
  
  
  BACKGROUND
  gromiha@iitm.ac.in
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors: Department of Biotechnology, Bhupat & Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600 036, India.
authors: Priyashree
authors: P
authors: Chaudhary
authors: Department of Biotechnology, Bhupat & Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600 036, India.
authors: Athi N
authors: AN
authors: Naganathan
authors: Department of Biotechnology, Bhupat & Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600 036, India.
authors: M Michael
authors: MM
authors: Gromiha
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D012984:Software
chemical_list: D000596:Amino Acids; D011506:Proteins