Modeling of loops in proteins: a multi-method approach

Jamroz, Michal; Kolinski, Andrzej
January 2010
BMC Structural Biology;2010, Vol. 10, p5
Academic Journal
Background: Template-target sequence alignment and loop modeling are key components of protein comparative modeling. Short loops can be predicted with high accuracy using structural fragments from other, not necessairly homologous proteins, or by various minimization methods. For longer loops multiscale approaches employing coarse-grained de novo modeling techniques should be more effective. Results: For a representative set of protein structures of various structural classes test predictions of loop regions have been performed using MODELLER, ROSETTA, and a CABS coarse-grained de novo modeling tool. Loops of various length, from 4 to 25 residues, were modeled assuming an ideal target-template alignment of the remaining portions of the protein. It has been shown that classical modeling with MODELLER is usually better for short loops, while coarse-grained de novo modeling is more effective for longer loops. Even very long missing fragments in protein structures could be effectively modeled. Resolution of such models is usually on the level 2-6 Ã…, which could be sufficient for guiding protein engineering. Further improvement of modeling accuracy could be achieved by the combination of different methods. In particular, we used 10 top ranked models from sets of 500 models generated by MODELLER as multiple templates for CABS modeling. On average, the resulting molecular models were better than the models from individual methods. Conclusions: Accuracy of protein modeling, as demonstrated for the problem of loop modeling, could be improved by the combinations of different modeling techniques.


Related Articles

  • Structure and function analysis of flexible alignment regions in proteins. Pirovano, Walter; Van der Reijden, Anneke; Feenstra, K. Anton; Heringa, Jaap // BMC Bioinformatics;2009 Supplement 13, Vol. 10, Special section p1 

    The article focuses on a study on the structural features and functional importance of flexible alignment regions in proteins. The role of structural alignment in defining gold standards for different bioinformatics applications is mentioned. According to the authors, the helices and coils...

  • COMA server for protein distant homology search. Margelevičius, Mindaugas; Laganeckas, Mindaugas; Venclovas, Česlovas // Bioinformatics;Aug2010, Vol. 26 Issue 15, p1905 

    Summary: Detection of distant homology is a widely used computational approach for studying protein evolution, structure and function. Here, we report a homology search web server based on sequence profile–profile comparison. The user may perform searches in one of several regularly...

  • HangOut: generating clean PSI-BLAST profiles for domains with long insertions. Kim, Bong-Hyun; Cong, Qian; Grishin, Nick V. // Bioinformatics;Jun2010, Vol. 26 Issue 12, p1564 

    Summary: Profile-based similarity search is an essential step in structure-function studies of proteins. However, inclusion of non-homologous sequence segments into a profile causes its corruption and results in false positives. Profile corruption is common in multidomain proteins, and single...

  • Critical assessment of structure-based sequence alignment methods at distant relationships. Kalaimathy, Singarevelu; Sowdhamini, Ramanathan; Kanagarajadurai, Karuppiah // Briefings in Bioinformatics;Mar2011, Vol. 12 Issue 2, p163 

    Accurate sequence alignments are crucial for modelling and to provide an evolutionary picture of related proteins. It is well-known that alignments are hard to obtain during distant relationships. Three thousand and fifty-two alignments of 218 pairs of protein domain structural entries, with...

  • Predicting β-turns and their types using predicted backbone dihedral angles and secondary structures. Kountouris, Petros; Hirst, Jonathan D. // BMC Bioinformatics;2010, Vol. 11, p407 

    Background: β-turns are secondary structure elements usually classified as coil. Their prediction is important, because of their role in protein folding and their frequent occurrence in protein chains. Results: We have developed a novel method that predicts β-turns and their types using...

  • The gputools package enables GPU computing in R. Buckner, Joshua; Wilson, Justin; Seligman, Mark; Athey, Brian; Watson, Stanley; Fan Meng // Bioinformatics;Jan2010, Vol. 26 Issue 1, p134 

    Motivation: By default, the R statistical environment does not make use of parallelism. Researchers may resort to expensive solutions such as cluster hardware for large analysis tasks. Graphics processing units (GPUs) provide an inexpensive and computationally powerful alternative. Using R and...

  • Mining protein loops using a structural alphabet and statistical exceptionality. Regad, Leslie; Martin, Juliette; Nuel, Gregory; Camproux, Anne-Claude // BMC Bioinformatics;2010, Vol. 11, p75 

    Background: Protein loops encompass 50% of protein residues in available three-dimensional structures. These regions are often involved in protein functions, e.g. binding site, catalytic pocket... However, the description of protein loops with conventional tools is an uneasy task. Regular...

  • HDAPD: a web tool for searching the disease-associated protein structures. Yi-Ruen Lin; Hsin-Yuan Wei; Tsung-Lin Tsai; Thy-Hou Lin // BMC Bioinformatics;2010, Vol. 11, p88 

    Background: The protein structures of the disease-associated proteins are important for proceeding with the structure-based drug design to against a particular disease. Up until now, proteins structures are usually searched through a PDB id or some sequence information. However, in the HDAPD...

  • Detection of distant evolutionary relationships between protein families using theory of sequence profile-profile comparison. Margelevicius, Mindaugas; Venclovas, Ceslovas // BMC Bioinformatics;2010, Vol. 11, p89 

    Background: Detection of common evolutionary origin (homology) is a primary means of inferring protein structure and function. At present, comparison of protein families represented as sequence profiles is arguably the most effective homology detection strategy. However, finding the best way to...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics