Transmembrane β-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 β-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 http://partiFold.csail.mit.edu/.
|Key words: outer membrane proteins, transmembrane β-barrels, residue contact, structure modeling, structure prediction, Boltzmann partition function, stochastic contact map, ensembles, sampling.|