Preferences help
enabled [disable] Abstract
Number of results
2010 | 57 | 1 | 125-133
Article title

TRACER. A new approach to comparative modeling that combines threading with free-space conformational sampling

Title variants
Languages of publication
A new approach to comparative modeling of proteins, TRACER, is described and benchmarked against classical modeling procedures. The new method unifies true three-dimensional threading with coarse-grained sampling of query protein conformational space. The initial sequence alignment of a query protein with a template is not required, although a template needs to be somehow identified. The template is used as a multi-featured fuzzy three-dimensional scaffold. The conformational search for the query protein is guided by intrinsic force field of the coarse-grained modeling engine CABS and by compatibility with the template scaffold. During Replica Exchange Monte Carlo simulations the model chain representing the query protein finds the best possible structural alignment with the template chain, that also optimizes the intra-protein interactions as approximated by the knowledge based force field of CABS. The benchmark done for a representative set of query/template pairs of various degrees of sequence similarity showed that the new method allows meaningful comparative modeling also for the region of marginal, or non-existing, sequence similarity. Thus, the new approach significantly extends the applicability of comparative modeling.
Physical description
  • Laboratory of Theory of Biopolymers, Faculty of Chemistry, University of Warsaw, Warszawa, Poland
  • Laboratory of Theory of Biopolymers, Faculty of Chemistry, University of Warsaw, Warszawa, Poland
  • Laboratory of Theory of Biopolymers, Faculty of Chemistry, University of Warsaw, Warszawa, Poland
  • Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25: 3389-3402.
  • Andreeva A, Prlic A, Hubbard TJ, Murzin AG (2007) SISYPHUS -structural alignments for proteins with non-trivial relationships. Nucleic Acids Res 35 (Database issue): D253-D259.
  • Chivian D, Baker D (2006) Homology modeling using parametric alignment ensemble generation with consensus and energy-based model selection. Nucleic Acids Res 34: e112.
  • Ekonomiuk D, Kielbasinski M, Kolinski A (2005) Protein modeling with reduced representation: statistical potentials and protein folding mechanism. Acta Biochim Pol 52: 741-758.
  • Eswar N, Eramian D, Webb B, Shen MY, Sali A (2008) Protein structure modeling with MODELLER. Methods Mol Biol 426: 145-159.
  • Geyer JC (1992) Practical Markov Chain Monte Carlo. Stat Sci 7: 473-483.
  • Hansmann UHE (1997) Parallel tempering algorithm for conformational studies of biological molecules. Chem Phys Lett 281: 140-150.
  • Henikoff S, Henikoff JG (1992) Amino acid substitution matrices from protein blocks. Proc Natl Acad Sci USA 89: 10915-10919.
  • Hukushima K, Nemoto K (1996) Exchange Monte Carlo Method and Application to Spin Glass Simulations. J Phys Soc Jpn 65: 1604-1608.
  • Kabsch W, Sander C (1983) Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 22: 2577-2637.
  • Kmiecik S, Kolinski A (2007) Characterization of protein-folding pathways by reduced-space modeling. Proc Natl Acad Sci USA 104: 12330-12335.
  • Kmiecik S, Kolinski A (2008) Folding pathway of the b1 domain of protein G explored by multiscale modeling. Biophys J 94: 726-736.
  • Kolinski A (2004) Protein modeling and structure prediction with a reduced representation. Acta Biochim Pol 51: 349-371.
  • Kolinski A, Bujnicki JM (2005) Generalized protein structure prediction based on combination of fold-recognition with de novo folding and evaluation of models. Proteins 61 (Suppl 7): 84-90.
  • Kolinski A, Gront D (2007) Comparative modeling without implicit sequence alignments. Bioinformatics 23: 2522-2527.
  • Kosinski J, Cymerman IA, Feder M, Kurowski MA, Sasin JM, Bujnicki JM (2003) A 'FRankenstein's monster' approach to comparative modeling: merging the finest fragments of Fold-Recognition models and iterative model refinement aided by 3D structure evaluation. Proteins 53 (Suppl 6): 369-379.
  • Kurcinski M, Kolinski A (2007) Steps towards flexible docking: modeling of three-dimensional structures of the nuclear receptors bound with peptide ligands mimicking co-activators' sequences. J Steroid Biochem Mol Biol 103: 357-360.
  • Kyte J, Doolittle RF (1982) A simple method for displaying the hydropathic character of a protein. J Mol Biol 157: 105-132.
  • Murzin AG, Brenner SE, Hubbard T, Chothia C (1995) SCOP: a structural classification of proteins database for the investigation of sequences and structures. J Mol Biol 247: 536-540.
  • Rohl CA, Strauss CE, Chivian D, Baker D (2004) Modeling structurally variable regions in homologous proteins with rosetta. Proteins 55: 656-677.
  • Rost B, Schneider R, Sander C (1997) Protein fold recognition by prediction-based threading. J Mol Biol 270: 471-480.
  • Sali A, Blundell TL (1993) Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol 234: 779-815.
  • Shen MY, Sali A (2006) Statistical potential for assessment and prediction of protein structures. Protein Sci 15: 2507-2524.
  • Swendsen RH, Wang JS (1986) Replica Monte Carlo Simulation of Spin Glasses. Phys Rev Lett 57: 2607-2609.
  • Zemla A (2003) LGA: A method for finding 3D similarities in protein structures. Nucleic Acids Res 31: 3370-3374.
  • Zemla A, Venclovas C, Moult J, Fidelis K (1999) Processing and analysis of CASP3 protein structure predictions. Proteins (Suppl 3): 22-29.
  • Zemla A, Zhou CE, Slezak T, Kuczmarski T, Rama D, Torres C, Sawicka D, Barsky D (2005) AS2TS system for protein structure modeling and analysis. Nucleic Acids Res 33 (Web Server issue): W111-115.
Document Type
Publication order reference
YADDA identifier
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.