Modeling Ensembles of Transmembrane Beta-barrel Proteins

Monday, January 14, 2008 - 2:35pm - 2:50pm
EE/CS 3-180
Jérôme Waldispühl (Massachusetts Institute of Technology)
Transmembrane beta-barrel (TMB) proteins are embedded in the outer membrane of
Gram-negative bacteria, mitochondria, and chloroplasts. Despite their
importance, very few nonhomologous TMB structures have been determined by X-ray
diffraction because of the experimental difficulty encountered in crystallizing
transmembrane proteins. We introduce the program partiFold to investigate the
folding landscape of TMBs. By computing the Boltzmann partition function,
partiFold estimates inter--strand residue interaction probabilities, predicts
contacts and per-residue X-ray crystal structure B-values, and samples
conformations from the Boltzmann low energy ensemble. This broad range of
predictive capabilities is achieved using a single, parameterizable grammatical
model to describe potential beta-barrel supersecondary structures, combined with
a novel energy function of stacked amino acid pair statistical potentials.
PartiFold outperforms existing programs for inter--strand residue contact
prediction on TMB proteins, offering both higher average predictive accuracy as
well as more consistent results. Moreover, the integration of these contact
probabilities inside a stochastic contact map can be used to infer a more
meaningful picture of the TMB folding landscape, which cannot be achieved with
other methods. Partifold's predictions of B-values are competitive with recent
methods specifically designed for this problem. Finally, we show that sampling
TMBs from the Boltzmann ensemble matches the X-ray crystal structure better
than single structure prediction methods. A webserver running partiFold is
available at

Joint work with: Charles W. O'Donnell, Srini Devadas, Peter Clote and Bonnie


[1] J. Waldispühl*, C.W. O'Donnel*, S. Devadas, P. Clote and B. Berger,
Modeling Ensembles of Transmembrane beta-barrel Proteins,
PROTEINS: Structure, Function and Bioinformatics, published online 14 Nov. 2007.

(* authors equally contributed)

[2]J. Waldispühl, B. Berger, P. Clote and J.-M. Steyaert,
Predicting Transmembrane beta-barrels and Inter-strand Residue Interactions from
PROTEINS: Structure, Function and Bioinformatics, vol. 65, issue 1, p.61-74,

MSC Code: