EFFICIENT CONSTRUCTION OF DISORDERED PROTEIN ENSEMBLES IN A BAYESIAN FRAMEWORK WITH OPTIMAL SELECTION OF CONFORMATIONS
Constructing an accurate model for the thermally accessible states of an Intrinsically Disordered Protein (IDP) is a fundamental problem in structural biology. This problem requires one to consider a large number of conformations in order to ensure that the model adequately represents the range of s...
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| Format: | Article |
| Language: | en_US |
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World Scientific Publishing
2017
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| Online Access: | http://hdl.handle.net/1721.1/111063 https://orcid.org/0000-0002-3415-242X |
| _version_ | 1826212189350920192 |
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| author | Fisher, Charles K Slavin, Orly Stultz, Collin M |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Fisher, Charles K Slavin, Orly Stultz, Collin M |
| author_sort | Fisher, Charles K |
| collection | MIT |
| description | Constructing an accurate model for the thermally accessible states of an Intrinsically Disordered Protein (IDP) is a fundamental problem in structural biology. This problem requires one to consider a large number of conformations in order to ensure that the model adequately represents the range of structures that the protein can adopt. Typically, one samples a wide range of structures in an attempt to obtain an ensemble that agrees with some pre-specified set of experimental data. However, models that contain more structures than the available experimental restraints are problematic as the large number of degrees of freedom in the ensemble leads to considerable uncertainty in the final model. We introduce a computationally efficient algorithm called Variational Bayesian Weighting with Structure Selection (VBWSS) for constructing a model for the ensemble of an IDP that contains a minimal number of conformations and, simultaneously, provides estimates for the uncertainty in properties calculated from the model. The algorithm is validated using reference ensembles and applied to construct an ensemble for the 140-residue IDP, monomeric α- synuclein. |
| first_indexed | 2024-09-23T15:17:46Z |
| format | Article |
| id | mit-1721.1/111063 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:17:46Z |
| publishDate | 2017 |
| publisher | World Scientific Publishing |
| record_format | dspace |
| spelling | mit-1721.1/1110632022-10-02T01:59:36Z EFFICIENT CONSTRUCTION OF DISORDERED PROTEIN ENSEMBLES IN A BAYESIAN FRAMEWORK WITH OPTIMAL SELECTION OF CONFORMATIONS Fisher, Charles K Slavin, Orly Stultz, Collin M Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Chemistry Slavin, Orly Stultz, Collin M Constructing an accurate model for the thermally accessible states of an Intrinsically Disordered Protein (IDP) is a fundamental problem in structural biology. This problem requires one to consider a large number of conformations in order to ensure that the model adequately represents the range of structures that the protein can adopt. Typically, one samples a wide range of structures in an attempt to obtain an ensemble that agrees with some pre-specified set of experimental data. However, models that contain more structures than the available experimental restraints are problematic as the large number of degrees of freedom in the ensemble leads to considerable uncertainty in the final model. We introduce a computationally efficient algorithm called Variational Bayesian Weighting with Structure Selection (VBWSS) for constructing a model for the ensemble of an IDP that contains a minimal number of conformations and, simultaneously, provides estimates for the uncertainty in properties calculated from the model. The algorithm is validated using reference ensembles and applied to construct an ensemble for the 140-residue IDP, monomeric α- synuclein. National Institutes of Health (U.S.) (Grant 5R21NS063185-02) 2017-08-29T19:30:01Z 2017-08-29T19:30:01Z 2011-12 Article http://purl.org/eprint/type/ConferencePaper 978-981-4596-37-4 978-981-4366-49-6 http://hdl.handle.net/1721.1/111063 Fisher, Charles K. et al. “EFFICIENT CONSTRUCTION OF DISORDERED PROTEIN ENSEMBLES IN A BAYESIAN FRAMEWORK WITH OPTIMAL SELECTION OF CONFORMATIONS.” Pacific Symposium on Biocomputing 2012 (December 2011): 82-93 https://orcid.org/0000-0002-3415-242X en_US http://dx.doi.org/10.1142/9789814366496_0009 Pacific Symposium on Biocomputing 2012 Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf World Scientific Publishing PMC |
| spellingShingle | Fisher, Charles K Slavin, Orly Stultz, Collin M EFFICIENT CONSTRUCTION OF DISORDERED PROTEIN ENSEMBLES IN A BAYESIAN FRAMEWORK WITH OPTIMAL SELECTION OF CONFORMATIONS |
| title | EFFICIENT CONSTRUCTION OF DISORDERED PROTEIN ENSEMBLES IN A BAYESIAN FRAMEWORK WITH OPTIMAL SELECTION OF CONFORMATIONS |
| title_full | EFFICIENT CONSTRUCTION OF DISORDERED PROTEIN ENSEMBLES IN A BAYESIAN FRAMEWORK WITH OPTIMAL SELECTION OF CONFORMATIONS |
| title_fullStr | EFFICIENT CONSTRUCTION OF DISORDERED PROTEIN ENSEMBLES IN A BAYESIAN FRAMEWORK WITH OPTIMAL SELECTION OF CONFORMATIONS |
| title_full_unstemmed | EFFICIENT CONSTRUCTION OF DISORDERED PROTEIN ENSEMBLES IN A BAYESIAN FRAMEWORK WITH OPTIMAL SELECTION OF CONFORMATIONS |
| title_short | EFFICIENT CONSTRUCTION OF DISORDERED PROTEIN ENSEMBLES IN A BAYESIAN FRAMEWORK WITH OPTIMAL SELECTION OF CONFORMATIONS |
| title_sort | efficient construction of disordered protein ensembles in a bayesian framework with optimal selection of conformations |
| url | http://hdl.handle.net/1721.1/111063 https://orcid.org/0000-0002-3415-242X |
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