title: Analysis of an optimal hidden Markov model for secondary structure prediction.
abstract: BACKGROUND
  Secondary structure prediction is a useful first step toward 3D structure prediction. A number of successful secondary structure prediction methods use neural networks, but unfortunately, neural networks are not intuitively interpretable. On the contrary, hidden Markov models are graphical interpretable models. Moreover, they have been successfully used in many bioinformatic applications. Because they offer a strong statistical background and allow model interpretation, we propose a method based on hidden Markov models.
  
  
  RESULTS
  Our HMM is designed without prior knowledge. It is chosen within a collection of models of increasing size, using statistical and accuracy criteria. The resulting model has 36 hidden states: 15 that model alpha-helices, 12 that model coil and 9 that model beta-strands. Connections between hidden states and state emission probabilities reflect the organization of protein structures into secondary structure segments. We start by analyzing the model features and see how it offers a new vision of local structures. We then use it for secondary structure prediction. Our model appears to be very efficient on single sequences, with a Q3 score of 68.8%, more than one point above PSIPRED prediction on single sequences. A straightforward extension of the method allows the use of multiple sequence alignments, rising the Q3 score to 75.5%.
  
  
  CONCLUSIONS
  The hidden Markov model presented here achieves valuable prediction results using only a limited number of parameters. It provides an interpretable framework for protein secondary structure architecture. Furthermore, it can be used as a tool for generating protein sequences with a given secondary structure content.
authors.affiliation: INSERM U726, Equipe de Bioinformatique Génomique et Moléculaire Université Denis Diderot Paris 7, 2 place jussieu, 75251 Paris Cedex 05, France. juliette.martin@jouy.inra.fr
authors.forename: Juliette
authors.initials: J
authors.lastname: Martin
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Gibrat
authors.forename: François
authors.initials: F
authors.lastname: Rodolphe
mesh_terms: D019295:Computational Biology / Q000379:methods*; D008390:Markov Chains; D008956:Models, Chemical; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*
chemical_list: D011506:Proteins