Systematic analysis of the effect of multiple templates on the accuracy of comparative models of protein structure

Chakravarty, Suvobrata; Godbole, Sucheta; Bing Zhang; Berger, Seth; Sanchez, Roberto
January 2008
BMC Structural Biology;2008, Vol. 8, Special section p1
Academic Journal
Background: Although multiple templates are frequently used in comparative modeling, the effect of inclusion of additional template(s) on model accuracy (when compared to that of corresponding single-template based models) is not clear. To address this, we systematically analyze two-template models, the simplest case of multiple-template modeling. For an existing target-template pair (single-template modeling), a two-template based model of the target sequence is constructed by including an additional template without changing the original alignment to measure the effect of the second template on model accuracy. Results: Even though in a large number of cases a two-template model showed higher accuracy than the corresponding one-template model, over the entire dataset only a marginal improvement was observed on average, as there were many cases where no change or the reverse change was observed. The increase in accuracy due to the structural complementarity of the templates increases at higher alignment accuracies. The combination of templates showing the highest potential for improvement is that where both templates share similar and low (less than 30%) sequence identity with the target, as well as low sequence identity with each other. The structural similarity between the templates also helps in identifying template combinations having a higher chance of resulting in an improved model. Conclusion: Inclusion of additional template(s) does not necessarily improve model quality, but there are distinct combinations of the two templates, which can be selected a priori, that tend to show improvement in model quality over the single template model. The benefit derived from the structural complementarity is dependent on the accuracy of the modeling alignment. The study helps to explain the observation that a careful selection of templates together with an accurate target:template alignment are necessary to the benefit from using multiple templates in comparative modeling and provides guidelines to maximize the benefit from using multiple templates. This enables formulation of simple template selection rules to rank targets of a protein family in the context of structural genomics.


Related Articles

  • Rapid Evolutionary Dynamics of Structural Disorder as a Potential Driving Force for Biological Divergence in Flaviviruses. Ortiz, Juan F.; MacDonald, Madolyn L.; Masterson, Patrick; Uversky, Vladimir N.; Siltberg-Liberles, Jessica // Genome Biology & Evolution;Mar2013, Vol. 5 Issue 3, p504 

    Protein structure is commonly regarded to be conserved and to dictate function. Most proteins rely on conformational flexibility to some degree. Are regions that convey conformational flexibility conserved over evolutionary time? Can changes in conformational flexibility alter protein function?...

  • Hidden conformations in protein structures. Ashkenazy, Haim; Unger, Ron; Kliger, Yossef // Bioinformatics;Jul2011, Vol. 27 Issue 14, p1941 

    Motivation: Prediction of interactions between protein residues (contact map prediction) can facilitate various aspects of 3D structure modeling. However, the accuracy of ab initio contact prediction is still limited. As structural genomics initiatives move ahead, solved structures of homologous...

  • Are the same or different amino acid residues responsible for correct and incorrect protein folding? Galzitskaya, O. V. // Biochemistry (00062979);Feb2009, Vol. 74 Issue 2, p186 

    It has been shown for 20 proteins that amino acid residues included into the protein folding nucleus, determined experimentally, are often involved in the theoretically determined amyloidogenic fragments. For 18 proteins, Φ-values indicative of the extent of residue involvement into the...

  • PFRES: protein fold classification by using evolutionary information and predicted secondary structure. Ke Chen; Lukasz Kurgan // Bioinformatics;Nov2007, Vol. 23 Issue 21, p2843 

    Motivation: The number of protein families has been estimated to be as small as 1000. Recent study shows that the growth in discovery of novel structures that are deposited into PDB and the related rate of increase of SCOP categories are slowing down. This indicates that the protein structure...

  • Trends in template/fragment-free protein structure prediction. Zhou, Yaoqi; Duan, Yong; Yang, Yuedong; Faraggi, Eshel; Lei, Hongxing // Theoretical Chemistry Accounts: Theory, Computation, & Modeling;Jan2011, Vol. 128 Issue 1, p3 

    Predicting the structure of a protein from its amino acid sequence is a long-standing unsolved problem in computational biology. Its solution would be of both fundamental and practical importance as the gap between the number of known sequences and the number of experimentally solved structures...

  • Modularity of Protein Folds as a Tool for Template-Free Modeling of Structures. Vallat, Brinda; Madrid-Aliste, Carlos; Fiser, Andras // PLoS Computational Biology;8/7/2015, Vol. 11 Issue 8, p1 

    Predicting the three-dimensional structure of proteins from their amino acid sequences remains a challenging problem in molecular biology. While the current structural coverage of proteins is almost exclusively provided by template-based techniques, the modeling of the rest of the protein...

  • DTA: dihedral transition analysis for characterization of the effects of large main-chain dihedral changes in proteins. Wataru Nishima; Guoying Qi; Steven Hayward; Akio Kitao // Bioinformatics;Mar2009, Vol. 25 Issue 5, p628 

    Motivation: The biological function of proteins is associated with a variety of motions, ranging from global domain motion to local motion of side chain. We propose a method, dihedral transition analysis (DTA), to identify significant dihedral angle changes between two distinct protein...

  • A sequence-based hybrid predictor for identifying conformationally ambivalent regions in proteins. Yu-Cheng Liu; Meng-Han Yang; Win-Li Lin; Chien-Kang Huang; Yen-Jen Oyang // BMC Genomics;2009 Supplement 3, Vol. 10, Special section p1 

    Background: Proteins are dynamic macromolecules which may undergo conformational transitions upon changes in environment. As it has been observed in laboratories that protein flexibility is correlated to essential biological functions, scientists have been designing various types of predictors...

  • Neural Network Pairwise Interaction Fields for Protein Model Quality Assessment and Ab Initio Protein Folding. Martin, Alberto J. M.; Mirabello, Claudio; Pollastri, Gianluca // Current Protein & Peptide Science;Sep2011, Vol. 12 Issue 6, p549 

    In order to use a predicted protein structure one needs to know how good it is, as the utility of a model depends on its quality. To this aim, many Model Quality Assessment Programs (MQAP) have been developed over the last decade, with MQAP also being assessed at the CASP competition. We present...


Read the Article


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

Try another library?
Sign out of this library

Other Topics