EFFICIENT CONSTRUCTION OF DISORDERED PROTEIN ENSEMBLES IN A BAYESIAN FRAMEWORK WITH OPTIMAL SELECTION OF CONFORMATIONS
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Stultz_Efficient construction.pdf
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Author(s)
Fisher, Charles K
Slavin, Orly
Stultz, Collin M
Date Issued
December 2011
Journal
Pacific Symposium on Biocomputing 2012
Publisher
World Scientific Publishing
Citation
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
Version
Author's final manuscript
Abstract
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.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1142/9789814366496_0009
