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Identifying the fold class of a protein sequence of unknown structure is a fundamental problem in modern biology. We apply a supervised learning algorithm to the classification of protein sequences with low sequence identity from a library of 174 structural classes created with the Combinatorial Extension structural alignment methodology. A class of rules is considered that assigns test sequences to structural classes based on the closest match of an amino acid index profile of the test sequence to a profile centroid for each class. A mathematical optimization procedure is applied to determine an amino acid index of maximal structural discriminatory power by maximizing the ratio of between-class to within-class profile variation. The optimal index is computed as the solution to a generalized eigenvalue problem, and its performance for fold classification is compared to that of other published indices. The optimal index has significantly more structural discriminatory power than all currently known indices, including average surrounding hydrophobicity, which it most closely resembles. It demonstrates >70% classification accuracy over all folds and nearly 100% accuracy on several folds with distinctive conserved structural features. Finally, there is a compelling universality to the optimal index in that it does not appear to depend strongly on the specific structural classes used in its computation. 相似文献
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Different genetic stains of avian RNA tumor virus (ATV) were labeled with the fluorescent membrane probe R-18 (rhodamine conjugated
to a hydrocarbon chain) and cellular receptors for virus infection were analyzed on a rapid, single-cell basis by a multiparameter
cell sorter. Chicken cells genetically susceptible to various R-18 ATV were found to adsorb much more virus, as measured by
increased fluorescent binding, than did genetically resistant chicken cells. Virus binding to receptor sites could be saturated
with increased concentrations of labeled virus. This binding could be altered by removal of the polycation, polybrene, indicating
the important influence of electrostatic forces. Correlated time measurements of virus binding to single cells were taken
with these fluorescence measurements allowing for a minute-to-minute study of the kinetics of viral adsorption to resistant
and susceptible cells. The ratio of fluorescence (proportional to the number of virions bound per cell) to light scatter (proportional
to cell surface area) on a cell-to-cell basis was analyzed to examine the heterogeneity in fluorescent virion bound per unit
cell surface area within a given cell type. With these calculations, it was found that a large amount, but not all, of observed
fluorescence heterogeneity merely reflects differences in cell surface areas. However, there are significant differences in
viral receptor site densities within this supposedly homogeneous population of cells. This study represents a successful application
of fluorescent membrane probes and flow cytometry to the study of cellular responses to viral infection at the single-cell
level. Sine large numbers of cells can be examined rapidly, small subpopulations of live virally susceptible or resistant
cells can be cloned by multiparameter cell sorting. 相似文献
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Marion H. OLeary William J. DeGooyer Thomas M. Dougherty Vernon Anderson 《Biochemical and biophysical research communications》1981,100(3):1320-1325
1-Hydroxycyclopropane carboxylic acid phosphate has been synthesized from diethyl succinate by acyloin condensation followed by ring contraction and phosphorylation. This compound is a potent competitive inhibitor of enzymes utilizing phosphoenolpyruvate. For phosphoenolpyruvate from maize, Ki = 7.3 μM at pH 8.0 in the presence of Mg2+. For pyruvate kinase, Ki = 2.0 mM at pH 7.0. For enolase, Ki = 8.0 μM at pH 8.0. In each case, this compound is a substantially better inhibitor than the commonly used phosphoenolpyruvate analogs phosphoglycolate and phospholactate, presumably because of the similarity in geometric and electronic structure between the cyclopropane compound and phosphoenolpyruvate. 相似文献
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Among Artiodactylamorpha, dichobunoids are some of the oldest fossil species that have been associated with Artiodactyla, the crown clade that includes hippopotamids, camelids, suoids, ruminants, and cetaceans. These important fossil species are known from early Eocene rocks of North America, Europe, and Asia, but their phylogenetic position has yet to be well resolved. Before generating such a phylogeny, it is first critical to document all of the anatomy of known dichobunoid fossils. Here we use CT scans to describe previously undescribed anatomy of the petrosal bone, a complex part of the mammalian skull that contains many variable and phylogenetically informative features. Results show that these extinct species share a number of features that are not documented in modern species including a lateral process of the epitympanic wing constituting the medial border of the piriform fenestra, and a tegmen tympani foramen that may have given passage to the ramus superior of the stapedial artery. Future comprehensive phylogenetic studies may show that many of these characters are plesiomophic for Artiodactylamopha. Some species (Diacodexis, Homacodon and ?Helohyus) exhibit a dorsolateral exposure of the mastoid region of the petrosal on the temporal part of the cranium. This uncommon feature has, to our knowledge, not been reported in another euungulate group. 相似文献