title: HHalign-Kbest: exploring sub-optimal alignments for remote homology comparative modeling.
abstract: BACKGROUND
  The HHsearch algorithm, implementing a hidden Markov model (HMM)-HMM alignment method, has shown excellent alignment performance in the so-called twilight zone (target-template sequence identity with ∼20%). However, an optimal alignment by HHsearch may contain small to large errors, leading to poor structure prediction if these errors are located in important structural elements.
  
  
  RESULTS
  HHalign-Kbest server runs a full pipeline, from the generation of suboptimal HMM-HMM alignments to the evaluation of the best structural models. In the HHsearch framework, it implements a novel algorithm capable of generating k-best HMM-HMM suboptimal alignments rather than only the optimal one. For large proteins, a directed acyclic graph-based implementation reduces drastically the memory usage. Improved alignments were systematically generated among the top k suboptimal alignments. To recognize them, corresponding structural models were systematically generated and evaluated with Qmean score. The method was benchmarked over 420 targets from the SCOP30 database. In the range of HHsearch probability of 20-99%, average quality of the models (TM-score) raised by 4.1-16.3% and 8.0-21.0% considering the top 1 and top 10 best models, respectively.
  
  
  METHODS
  http://bioserv.rpbs.univ-paris-diderot.fr/services/HHalign-Kbest/ (source code and server).
  
  
  BACKGROUND
  guerois@cea.fr.
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, University Paris-Saclay, CEA-Saclay, 91191 Gif-sur-Yvette.
authors.forename: Jinchao
authors.initials: J
authors.lastname: Yu
authors.affiliation: INSERM U973, MTi, F-75205 Paris, Université Paris Diderot, Sorbonne Paris Cité F-75205 Paris and Ressource Parisienne en Bioinformatique Structurale, F-75205 Paris, France.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Picord
authors.affiliation: INSERM U973, MTi, F-75205 Paris, Université Paris Diderot, Sorbonne Paris Cité F-75205 Paris and Ressource Parisienne en Bioinformatique Structurale, F-75205 Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Tuffery
authors.affiliation: Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, University Paris-Saclay, CEA-Saclay, 91191 Gif-sur-Yvette.
authors.forename: Raphael
authors.initials: R
authors.lastname: Guerois
mesh_terms: D000465:Algorithms; D008390:Markov Chains; D008958:Models, Molecular; D016415:Sequence Alignment / Q000379:methods*; D020539:Sequence Analysis, Protein; D012984:Software; D040681:Structural Homology, Protein