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Motivation: Large-scale conformational changes in proteins are implicated in many important biological functions. These structural transitions can often be rationalized in terms of relative movements of rigid domains. There is a need for objective and automated methods that identify rigid domains in sets of protein structures showing alternative conformational states. Results: We present a probabilistic model for detecting rigid-body movements in protein structures. Our model aims to approximate alternative conformational states by a few structural parts that are rigidly transformed under the action of a rotation and a translation. By using Bayesian inference and Markov chain Monte Carlo sampling, we estimate all parameters of the model, including a segmentation of the protein into rigid domains, the structures of the domains themselves, and the rigid transformations that generate the observed structures. We find that our Gibbs sampling algorithm can also estimate the optimal number of rigid domains with high efficiency and accuracy. We assess the power of our method on several thousand entries of the DynDom database and discuss applications to various complex biomolecular systems. [ABSTRACT FROM AUTHOR]

Objectives Rebamipide, a novel anti-ulcer agent, is listed in biopharmaceutics classification class IV because of its low aqueous solubility and permeability. Consequently, the bioavailability of rebamipide is under 10% in humans. The aim of this study was to increase the solubility and determine the effect of solubility enhancement on the bioavailability and efficacy of rebamipide (RBM). Methods After taking into account the physiochemical properties of RBM (solubility, melting point, dosage etc.), solid dispersion was chosen as the solubility enhancement method. A rebamipide solid dispersion system containing the drug, l-lysine, PVP-VA 64 and poloxamer 407 was obtained from a spray-drying method. Solubility enhancement of RBM from the solid dispersion was determined by a dissolution test in 900 ml at pH 1.2. The bioavailability and efficacy of RBM solid dispersion were evaluated in a rat model. Key findings The aqueous solubility of RBM was improved 62.17 times by solid dispersion. The oral bioavailability of the drug was also increased 1.74-fold from solid dispersion compared with the reference product in a rat model. With regard to the anti-ulcer effect, the percentage inhibition of the solid dispersion was 2.71 times higher than that of the reference product in the ulcer-induced rat model. Conclusions A solid dispersion of rebamipide was successfully formulated using the spray-drying method. Bioavailability and efficacy of rebamipide were increased significantly by solubility enhancement of the drug. [ABSTRACT FROM AUTHOR]