H. Chandola, A.K. Yan, S. Potluri, B.R. Donald, and C. Bailey-Kellogg, "NMR structural inference of symmetric homo-oligomers", J. Comp. Biol., 2011, 18:1757-1775. [paper]

Symmetric homo-oligomers represent a majority of proteins, and determining their structures helps elucidate important biological processes including ion transport, signal transduction, and transcriptional regulation. In order to account for the noise and sparsity in the distance restraints used in NMR structure determination of cyclic (Cn) symmetric homo-oligomers, and the resulting uncertainty in the determined structures, we develop a Bayesian structural inference approach. In contrast to traditional NMR structure determination methods, which identify a small set of low-energy conformations, the inferential approach characterizes the entire posterior distribution of conformations. Unfortunately, traditional stochastic techniques for inference may under-sample the rugged landscape of the posterior, missing important contributions from high-quality individual conformations and not accounting for the possible aggregate effects on inferred quantities from numerous unsampled conformations. However, by exploiting the geometry of symmetric homo-oligomers, we develop an algorithm that provides provable guarantees for the posterior distribution and the inferred mean atomic coordinates. Using experimental restraints for three proteins, we demonstrate that our approach is able to objectively characterize the structural diversity supported by the data. By simulating spurious and missing restraints, we further demonstrate that our approach is robust, degrading smoothly with noise and sparsity.

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