title: A conservation and rigidity based method for detecting critical protein residues.
abstract: BACKGROUND
  Certain amino acids in proteins play a critical role in determining their structural stability and function. Examples include flexible regions such as hinges which allow domain motion, and highly conserved residues on functional interfaces which allow interactions with other proteins. Detecting these regions can aid in the analysis and simulation of protein rigidity and conformational changes, and helps characterizing protein binding and docking. We present an analysis of critical residues in proteins using a combination of two complementary techniques. One method performs in-silico mutations and analyzes the protein's rigidity to infer the role of a point substitution to Glycine or Alanine. The other method uses evolutionary conservation to find functional interfaces in proteins.
  
  
  RESULTS
  We applied the two methods to a dataset of proteins, including biomolecules with experimentally known critical residues as determined by the free energy of unfolding. Our results show that the combination of the two methods can detect the vast majority of critical residues in tested proteins.
  
  
  CONCLUSIONS
  Our results show that the combination of the two methods has the potential to detect more information than each method separately. Future work will provide a confidence level for the criticalness of a residue to improve the accuracy of our method and eliminate false positives. Once the combined methods are integrated into one scoring function, it can be applied to other domains such as estimating functional interfaces.
authors.forename: Bahar
authors.initials: B
authors.lastname: Akbal-Delibas
authors.forename: Filip
authors.initials: F
authors.lastname: Jagodzinski
authors.forename: Nurit
authors.initials: N
authors.lastname: Haspel
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000596:Amino Acids; D019295:Computational Biology / Q000379:methods*; D017124:Conserved Sequence; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D011485:Protein Binding; D011487:Protein Conformation; D055550:Protein Stability; D058767:Protein Unfolding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D012984:Software
chemical_list: D000596:Amino Acids; D011506:Proteins