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Monastyrskyy B.,University of California at Davis | Kryshtafovych A.,University of California at Davis | Moult J.,University of Maryland Biotechnology Institute | Tramontano A.,University of Rome La Sapienza | Fidelis K.,University of California at Davis
Proteins: Structure, Function and Bioinformatics | Year: 2014

The article presents the assessment of disorder region predictions submitted to CASP10. The evaluation is based on the three measures tested in previous CASPs: (i) balanced accuracy, (ii) the Matthews correlation coefficient for the binary predictions, and (iii) the area under the curve in the receiver operating characteristic (ROC) analysis of predictions using probability annotation. We also performed new analyses such as comparison of the submitted predictions with those obtained with a Naïve disorder prediction method and with predictions from the disorder prediction databases D2P2 and MobiDB. On average, the methods participating in CASP10 demonstrated slightly better performance than those in CASP9. © 2013 Wiley Periodicals, Inc.

Vagin A.,University of York | Teplyakov A.,University of Maryland Biotechnology Institute | Teplyakov A.,Centocor R and D Inc.
Acta Crystallographica Section D: Biological Crystallography | Year: 2010

MOLREP is an automated program for molecular replacement that utilizes a number of original approaches to rotational and translational search and data preparation. Since the first publication describing the program, MOLREP has acquired a variety of features that include weighting of the X-ray data and search models, multi-copy search, fitting the model into electron density, structural superposition of two models and rigid-body refinement. The program can run in a fully automatic mode using optimized parameters calculated from the input data. © 2010 International Union of Crystallography Printed in Singapore - all rights reserved.

Hnizdo V.,U.S. National Institute for Occupational Safety and Health | Gilson M.K.,University of Maryland Biotechnology Institute
Entropy | Year: 2010

The differential Shannon entropy of information theory can change under a change of variables (coordinates), but the thermodynamic entropy of a physical system must be invariant under such a change. This difference is puzzling, because the Shannon and Gibbs entropies have the same functional form. We show that a canonical change of variables can, indeed, alter the spatial component of the thermodynamic entropy just as it alters the differential Shannon entropy. However, there is also a momentum part of the entropy, which turns out to undergo an equal and opposite change when the coordinates are transformed, so that the total thermodynamic entropy remains invariant. We furthermore show how one may correctly write the change in total entropy for an isothermal physical process in any set of spatial coordinates. © 2010 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.

Monastyrskyy B.,University of California at Davis | Fidelis K.,University of California at Davis | Moult J.,University of Maryland Biotechnology Institute | Tramontano A.,University of Rome La Sapienza | Kryshtafovych A.,University of California at Davis
Proteins: Structure, Function and Bioinformatics | Year: 2011

Lack of stable three-dimensional structure, or intrinsic disorder, is a common phenomenon in proteins. Naturally, unstructured regions are proven to be essential for carrying function by many proteins, and therefore identification of such regions is an important issue. CASP has been assessing the state of the art in predicting disorder regions from amino acid sequence since 2002. Here, we present the results of the evaluation of the disorder predictions submitted to CASP9. The assessment is based on the evaluation measures and procedures used in previous CASPs. The balanced accuracy and the Matthews correlation coefficient were chosen as basic measures for evaluating the correctness of binary classifications. The area under the receiver operating characteristic curve was the measure of choice for evaluating probability-based predictions of disorder. The CASP9 methods are shown to perform slightly better than the CASP7 methods but not better than the methods in CASP8. It was also shown that capability of most CASP9 methods to predict disorder decreases with increasing minimum disorder segment length. © 2011 Wiley-Liss, Inc.

Gilson M.K.,University of Maryland Biotechnology Institute | Gilson M.K.,La jolla Pharmaceutical
Journal of Chemical Theory and Computation | Year: 2010

Changes in mechanical stresses in a tight-binding host-guest system were computed and visualized as the cation was computationally pulled out of the cucurbituril host in a series of steps. A sharp conformational transition was observed as one of the guests ammonium groups jumped through the center of the host to the opposite portal. The conformation immediately prior to this transition was found to possess high levels of Lennard-Jones and electrostatic stress. This observation, along with the specific distribution of Lennard-Jones stress around the portals, suggested that the conformational transition resulted from steric constriction, which had been expected, and electrostatics, which was not expected. An important role for electrostatics, at least at the level of these calculations, was confirmed by a comparative computational pulling study of another guest molecule lacking the critical ammonium group. These calculations suggest that the binding kinetics of diammonium guests that position an ammonium at each cucurbituril portal will be found to be slower than the kinetics of monoammonium guests. More generally, the results suggest that computational stress analysis can provide mechanistic insight into supramolecular systems. It will be of considerable interest to extend such applications to biomolecules, for which the mechanisms of conformational change are of great scientific and practical interest. Copyright © 2010 American Chemical Society.

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