Homology-based modeling of 3D structures of protein-protein complexes using alignments of modified sequence profiles. Export

@article{kundrotas_2008_homologybased, abstract = {Customary practice in predicting 3D structures of protein-protein complexes is employment of various docking methods when the structures of separate monomers are known a priori. The alternative approach, i.e. the template-based prediction with pure sequence information as a starting point, is still considered as being inferior mostly due to presumption that the pool of available structures of protein-protein complexes, which can serve as putative templates, is not sufficiently large. Recently, however, several labs have developed databases containing thousands of 3D structures of protein-protein complexes, which enable statistically reliable testing of homology-based algorithms. In this paper we report the results on homology-based modeling of 3D structures of protein complexes using alignments of modified sequence profiles. The method, called HOMology-BAsed COmplex Prediction (HOMBACOP), has two distinctive features: (I) extra weight on aligning interfacial residues in the dynamical programming algorithm, and (II) increased gap penalties for the interfacial segments. The method was tested against our recently developed ProtCom database and against the Boston University protein-protein BENCHMARK. In both cases, models generated were compared to the models built on basis of customarily protein structure initiative (PSI)-BLAST sequence alignments. It was found that existence of homologous (by the means of PSI-BLAST) templates (44\% of cases) enables both methods to produce models of good quality, with the profiles method outperforming the PSI-BLAST models (with respect to the percentage of correctly predicted residues on the complex interface and fraction of native interfacial contacts). The models were evaluated according to the CAPRI assessment criteria and about two thirds of the models were found to fall into acceptable and medium-quality categories. The same comparison of a larger set of 463 protein complexes showed again that profiles generate better models. We further demonstrate, using our ProtCom database, the suitability of the profile alignment algorithm in detecting remote homologues between query and template sequences, where the PSI-BLAST method fails.}, address = {Computational Biophysics and Bioinformatics, Department of Physics, Clemson University, Clemson, SC 29634, United States.}, author = {Kundrotas, Petras J J. and Lensink, Marc F F. and Alexov, Emil}, citeulike-article-id = {2941194}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.ijbiomac.2008.05.004}, citeulike-linkout-1 = {http://linkinghub.elsevier.com/retrieve/pii/S0141813008001062}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18572239}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18572239}, day = {21}, doi = {10.1016/j.ijbiomac.2008.05.004}, issn = {0141-8130}, journal = {International journal of biological macromolecules}, keywords = {algorithm, alignment, binding, complexes, data\_integration, modelling, proj\_assembly, structure}, month = {May}, posted-at = {2008-06-29 11:15:36}, priority = {2}, title = {Homology-based modeling of 3D structures of protein-protein complexes using alignments of modified sequence profiles.}, url = {http://dx.doi.org/10.1016/j.ijbiomac.2008.05.004}, year = {2008} }

TY - JOUR ID - kundrotas_2008_homologybased L3 - citeulike-article-id:2941194 N2 - Customary practice in predicting 3D structures of protein-protein complexes is employment of various docking methods when the structures of separate monomers are known a priori. The alternative approach, i.e. the template-based prediction with pure sequence information as a starting point, is still considered as being inferior mostly due to presumption that the pool of available structures of protein-protein complexes, which can serve as putative templates, is not sufficiently large. Recently, however, several labs have developed databases containing thousands of 3D structures of protein-protein complexes, which enable statistically reliable testing of homology-based algorithms. In this paper we report the results on homology-based modeling of 3D structures of protein complexes using alignments of modified sequence profiles. The method, called HOMology-BAsed COmplex Prediction (HOMBACOP), has two distinctive features: (I) extra weight on aligning interfacial residues in the dynamical programming algorithm, and (II) increased gap penalties for the interfacial segments. The method was tested against our recently developed ProtCom database and against the Boston University protein-protein BENCHMARK. In both cases, models generated were compared to the models built on basis of customarily protein structure initiative (PSI)-BLAST sequence alignments. It was found that existence of homologous (by the means of PSI-BLAST) templates (44% of cases) enables both methods to produce models of good quality, with the profiles method outperforming the PSI-BLAST models (with respect to the percentage of correctly predicted residues on the complex interface and fraction of native interfacial contacts). The models were evaluated according to the CAPRI assessment criteria and about two thirds of the models were found to fall into acceptable and medium-quality categories. The same comparison of a larger set of 463 protein complexes showed again that profiles generate better models. We further demonstrate, using our ProtCom database, the suitability of the profile alignment algorithm in detecting remote homologues between query and template sequences, where the PSI-BLAST method fails. JF - International journal of biological macromolecules SN - 0141-8130 AD - Computational Biophysics and Bioinformatics, Department of Physics, Clemson University, Clemson, SC 29634, United States. TI - Homology-based modeling of 3D structures of protein-protein complexes using alignments of modified sequence profiles. KW - algorithm KW - alignment KW - binding KW - complexes KW - data_integration KW - modelling KW - proj_assembly KW - structure AU - Kundrotas, Petras J AU - Lensink, Marc F AU - Alexov, Emil PY - 2008/05/21/ UR - http://dx.doi.org/10.1016/j.ijbiomac.2008.05.004 ER -