title: Fast and accurate predictions of protein stability changes upon mutations using statistical potentials and neural networks: PoPMuSiC-2.0.
abstract: BACKGROUND
  The rational design of proteins with modified properties, through amino acid substitutions, is of crucial importance in a large variety of applications. Given the huge number of possible substitutions, every protein engineering project would benefit strongly from the guidance of in silico methods able to predict rapidly, and with reasonable accuracy, the stability changes resulting from all possible mutations in a protein.
  
  
  RESULTS
  We exploit newly developed statistical potentials, based on a formalism that highlights the coupling between four protein sequence and structure descriptors, and take into account the amino acid volume variation upon mutation. The stability change is expressed as a linear combination of these energy functions, whose proportionality coefficients vary with the solvent accessibility of the mutated residue and are identified with the help of a neural network. A correlation coefficient of R = 0.63 and a root mean square error of sigma(c) = 1.15 kcal/mol between measured and predicted stability changes are obtained upon cross-validation. These scores reach R = 0.79, and sigma(c) = 0.86 kcal/mol after exclusion of 10% outliers. The predictive power of our method is shown to be significantly higher than that of other programs described in the literature.
  
  
  BACKGROUND
  http://babylone.ulb.ac.be/popmusic
authors: Bioinformatique génomique et structurale, Université Libre de Bruxelles. Av Fr. Roosevelt 50, CP165/61, 1050 Brussels, Belgium. ydehouck@ulb.ac.be
authors: Yves
authors: Y
authors: Dehouck
authors: Aline
authors: A
authors: Grosfils
authors: Benjamin
authors: B
authors: Folch
authors: Dimitri
authors: D
authors: Gilis
authors: Philippe
authors: P
authors: Bogaerts
authors: Marianne
authors: M
authors: Rooman
mesh_terms: D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D009154:Mutation; D016571:Neural Networks, Computer; D017510:Protein Folding; D055550:Protein Stability; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D020539:Sequence Analysis, Protein
chemical_list: D011506:Proteins