Abstract
The majority of proteins function when associated in multimolecular assemblies. Yet, prediction of the structures of multimolecular complexes has largely not been addressed, probably due to the magnitude of the combinatorial complexity of the problem. Docking applications have traditionally been used to predict pairwise interactions between molecules. We have developed an algorithm that extends the application of docking to multimolecular assemblies. We apply it to predict quaternary structures of both oligomers and multi-protein complexes. The algorithm predicted well a near-native arrangement of the input subunits for all cases in our data set, where the number of the subunits of the different target complexes varied from three to ten. In order to simulate a more realistic scenario, unbound cases were tested. In these cases the input conformations of the subunits are either unbound conformations of the subunits or a model obtained by a homology modeling technique. The successful predictions of the unbound cases, where the input conformations of the subunits are different from their conformations within the target complex, suggest that the algorithm is robust. We expect that this type of algorithm should be particularly useful to predict the structures of large macromolecular assemblies, which are difficult to solve by experimental structure determination.
Original language | English |
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Pages (from-to) | 435-447 |
Number of pages | 13 |
Journal | Journal of Molecular Biology |
Volume | 349 |
Issue number | 2 |
DOIs | |
Publication status | Published - Jun 3 2005 |
Bibliographical note
Funding Information:We thank Dina Schneidman-Duhovny for numerous discussions and useful advice. This research has been supported, in part, by the “Center of Excellence in Geometric Computing and its Applications” funded by the Israel Science Foundation (administered by the Israel Academy of Sciences). The research of H.J.W. has been supported partially by the Hermann Minkowski-Minerva Center for Geometry at Tel Aviv University. The research of Y.I. and H.B. has been supported by the Eshkol Fellowship funded by the Israeli Ministry of Science. The research of R. Nussinov has been funded in whole or in part, with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number NO1-CO-12400. The content of this publication does not necessarily reflect the view or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organization imply endorsement by the U.S. Government.
Funding
We thank Dina Schneidman-Duhovny for numerous discussions and useful advice. This research has been supported, in part, by the “Center of Excellence in Geometric Computing and its Applications” funded by the Israel Science Foundation (administered by the Israel Academy of Sciences). The research of H.J.W. has been supported partially by the Hermann Minkowski-Minerva Center for Geometry at Tel Aviv University. The research of Y.I. and H.B. has been supported by the Eshkol Fellowship funded by the Israeli Ministry of Science. The research of R. Nussinov has been funded in whole or in part, with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number NO1-CO-12400. The content of this publication does not necessarily reflect the view or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organization imply endorsement by the U.S. Government.
Funders | Funder number |
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Hermann Minkowski-Minerva Center for Geometry | |
Israeli Ministry of Science | |
National Institutes of Health | NO1-CO-12400 |
National Cancer Institute | Z01BC010442 |
Academy of Leisure Sciences | |
Israel Science Foundation | |
Tel Aviv University |
ASJC Scopus Subject Areas
- Biophysics
- Structural Biology
- Molecular Biology