Constructing templates for protein structure prediction by simulation of protein folding pathways

@article{citeulike:2714705, abstract = {How a one-dimensional protein sequence folds into a specific 3D structure remains a difficult challenge in structural biology. Many computational methods have been developed in an attempt to predict the tertiary structure of the protein; most of these employ approaches that are based on the accumulated knowledge of solved protein structures. Here we introduce a novel and fully automated approach for predicting the 3D structure of a protein that is based on the well accepted notion that protein folding is a hierarchical process. Our algorithm follows the hierarchical model by employing two stages: the first aims to find a match between the sequences of short independently-folding structural entities and parts of the target sequence and assigns the respective structures. The second assembles these local structural parts into a complete 3D structure, allowing for long-range interactions between them. We present the results of applying our method to a subset of the targets from CASP6 and CASP7. Our results indicate that for targets with a significant sequence similarity to known structures we are often able to provide predictions that are better than those achieved by two leading servers, and that the most significant improvements in comparison with these methods occur in regions of a gapped structural alignment between the native structure and the closest available structural template. We conclude that in addition to performing well for targets with known homologous structures, our method shows great promise for addressing the more general category of comparative modeling targets, which is our next goal. Proteins 2008. {\copyright} 2008 Wiley-Liss, Inc.}, address = {School of Computer Science, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 69978, Israel; Basic Research Program, SAIC-Frederick, Inc., Center for Cancer Research, Nanobiology Program, NCI, Frederick, Maryland 21702; Department of Human Genetics and Molecular Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel}, author = {Kifer, Ilona and Nussinov, Ruth and Wolfson, Haim J. }, citeulike-article-id = {2714705}, doi = {10.1002/prot.22073}, journal = {Proteins: Structure, Function, and Bioinformatics}, keywords = {folding, modelling, prediction, protein, simulation, structure}, number = {9999}, pages = {NA+}, posted-at = {2008-04-25 01:52:40}, priority = {2}, title = {Constructing templates for protein structure prediction by simulation of protein folding pathways}, url = {http://dx.doi.org/10.1002/prot.22073}, volume = {9999}, year = {2008} }

TY - JOUR ID - citeulike:2714705 L3 - citeulike-article-id:2714705 TI - Constructing templates for protein structure prediction by simulation of protein folding pathways JF - Proteins: Structure, Function, and Bioinformatics VL - 9999 IS - 9999 SP - NA AD - School of Computer Science, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 69978, Israel; Basic Research Program, SAIC-Frederick, Inc., Center for Cancer Research, Nanobiology Program, NCI, Frederick, Maryland 21702; Department of Human Genetics and Molecular Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel N2 - How a one-dimensional protein sequence folds into a specific 3D structure remains a difficult challenge in structural biology. Many computational methods have been developed in an attempt to predict the tertiary structure of the protein; most of these employ approaches that are based on the accumulated knowledge of solved protein structures. Here we introduce a novel and fully automated approach for predicting the 3D structure of a protein that is based on the well accepted notion that protein folding is a hierarchical process. Our algorithm follows the hierarchical model by employing two stages: the first aims to find a match between the sequences of short independently-folding structural entities and parts of the target sequence and assigns the respective structures. The second assembles these local structural parts into a complete 3D structure, allowing for long-range interactions between them. We present the results of applying our method to a subset of the targets from CASP6 and CASP7. Our results indicate that for targets with a significant sequence similarity to known structures we are often able to provide predictions that are better than those achieved by two leading servers, and that the most significant improvements in comparison with these methods occur in regions of a gapped structural alignment between the native structure and the closest available structural template. We conclude that in addition to performing well for targets with known homologous structures, our method shows great promise for addressing the more general category of comparative modeling targets, which is our next goal. Proteins 2008. © 2008 Wiley-Liss, Inc. KW - folding KW - modelling KW - prediction KW - protein KW - simulation KW - structure AU - Kifer, Ilona AU - Nussinov, Ruth AU - Wolfson, Haim PY - 2008/// UR - http://dx.doi.org/10.1002/prot.22073 ER -