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The functional and biological significance of selected CASP13 targets are described by the authors of the structures. The structural biologists discuss the most interesting structural features of the target proteins and assess whether these features were correctly reproduced in the predictions submitted to the CASP13 experiment.

[Purpose/Significance] This paper aimed at evaluating information exchange efficiency of fire-fighting microblogs, in order to guiding information exchange and promoting the information exchange efficiency in emergency management. There are two primary innovations in this paper. First, compared with the existing research on emergency management and DEA methods, the existing research on the application of government microblogs in emergency management mainly focused on qualitative research. The research on DEA method focused on the performance evaluation of enterprises and banks. This paper used the DEA method to quantitatively analyze the efficiency of information exchange in emergency management. Second, this paper used the DEA method to divide the efficiency of fire-fighting microblogs into two parts: DEA effective and non-DEA effective, and comprehensively explored measures to improve efficiency from these two parts. [Method/Process] This paper took the highest level of fire-fighting microblogs officially certified by the provinces, autonomous regions and municipalities as the research resources. In order to do this research, an indicator system based on current influence of government microblog and the efficiency of communication was constructed; DEA-BBC model was used to measure the efficiency of fire-fighting microblog information exchange; the micro and macro influencing factors of fire-fighting microblog information exchange efficiency were identified; finally some measures were put forward to improve the efficiency of information exchange on fire-fighting microblogging. DEA is a non-parametric test method commonly used for enterprise performance and efficiency evaluation in management science. It can be used to evaluate decision-making units of multiple input indicators and multiple output indicators. Beyond that, the decision-making results of the method are not affected by the dimensions of input indicators and output indicators. This method also does not need to make weight assumptions, so it can provide more objective analysis results to make contribution to refining more effective improvement measures. [Results/Conclusions] The information exchange efficiency of the fire-fighting microblogs was generally rated as the medium level. It is better for us to arrange various inputs of the microblog account reasonably, and make full use of resources, which could improve the efficiency of information exchange. In addition, the operation of fire-fighting microblogs in different regions should be based on regional characteristics and period characteristics; local governments ought to strengthen network infrastructure construction and resource investment to eliminate the "digital divide"; government agencies should improve management systems, standardize the words and deeds of netizens and the daily work of relevant personnel. Microblog plays an important role in emergency management, which is also a necessary condition for the vigorous development of China's Internet governance.

The kinetic properties of an E232Q variant of the xanthine dehydrogenase from Rhodobacter capsulatus have been examined to ascertain whether Glu(232) in wild-type enzyme is protonated or unprotonated in the course of catalysis at neutral pH. We find that kred, the limiting rate constant for reduction at high [xanthine], is significantly compromised in the variant, a result that is inconsistent with Glu(232) being neutral in the active site of the wild-type enzyme. A comparison of the pH dependence of both kred and kred/Kd from reductive half-reaction experiments between wild-type and enzyme and the E232Q variant suggests that the ionized Glu(232) of wild-type enzyme plays an important role in catalysis by discriminating against the monoanionic form of substrate, effectively increasing the pKa of substrate by two pH units and ensuring that at physiological pH the neutral form of substrate predominates in the Michaelis complex. A kinetic isotope study of the wild-type R. capsulatus enzyme indicates that, as previously determined for the bovine and chicken enzymes, product release is principally rate-limiting in catalysis. The disparity in rate constants for the chemical step of the reaction and product release, however, is not as great in the bacterial enzyme as compared with the vertebrate forms. The results indicate that the bacterial and bovine enzymes catalyze the chemical step of the reaction to the same degree and that the faster turnover observed with the bacterial enzyme is due to a faster rate constant for product release than is seen with the vertebrate enzyme.

Xanthine oxidase is a molybdenum-containing hydroxylase that catalyzes the hydroxylation of sp2-hybridized carbon centers in a variety of aromatic heterocycles as well as aldehydes. Crystal structures of die oxidase form of the bovine enzyme in complex with a poor substrate indole-3-acetaldehyde and the nonsubstrate guanine have been determined, both at a resolution of 1.6 Å. In each structure, a specific and unambiguous orientation of the substrate in the active site is observed in which the hydroxylatable site is oriented away from the active site molybdenum center. The orientation seen with indole-3-acetaldehyde has the substrate positioned with the indole ring rather than the exocyclic aldehyde nearest the molybdenum center, indicating that the substrate must rotate some 30° in the enzyme active site to permit hydroxylation of the aldehyde group (as observed experimentally), accounting for the reduced reactivity of the enzyme toward this substrate. The principal product of hydroxylation of indole-3-acetaldehyde by the bovine enzyme is confirmed to be indole-3-carboxylic acid based on its characteristic UV-vis spectrum, and the kinetics of enzyme reduction are reported. With guanine, the dominant orientation seen crystallographically has the C-S position that might be hydroxylated pointed away from the active site molybdenum center, in a configuration resembling that seen previously with hypoxanthine (a substrate that is effectively hydroxylated at position 2). The ∼180° reorientation required to permit reaction is sterically prohibited, indicating that substrate (mis)orientation in the active site is a major factor precluding formation of the highly mutagenic 8-hydroxyguanine. [ABSTRACT FROM AUTHOR]

Computational approaches for predicting protein-ligand interactions can facilitate drug lead discovery and drug target determination. We have previously developed a threading/structural-based approach, FINDSITE comb , for the virtual ligand screening of proteins that has been extensively experimentally validated. Even when low resolution predicted protein structures are employed, FINDSITE comb has the advantage of being faster and more accurate than traditional high-resolution structure-based docking methods. It also overcomes the limitations of traditional QSAR methods that require a known set of seed ligands that bind to the given protein target. Here, we further improve FINDSITE comb by enhancing its template ligand selection from the PDB/DrugBank/ChEMBL libraries of known protein-ligand interactions by (1) parsing the template proteins and their corresponding binding ligands in the DrugBank and ChEMBL libraries into domains so that the ligands with falsely matched domains to the targets will not be selected as template ligands; (2) applying various thresholds to filter out falsely matched template structures in the structure comparison process and thus their corresponding ligands for template ligand selection. With a sequence identity cutoff of 30% of target to templates and modeled target structures, FINDSITE comb2.0 is shown to significantly improve upon FINDSITE comb on the DUD-E benchmark set by increasing the 1% enrichment factor from 16.7 to 22.1, with a p-value of 4.3 × 10 -3 by the Student t-test. With an 80% sequence identity cutoff of target to templates for the DUD-E set and modeled target structures, FINDSITE comb2.0 , having a 1% ROC enrichment factor of 52.39, also outperforms state-of-the-art methods that employ machine learning such as a deep convolutional neural network, CNN, with an enrichment of 29.65. Thus, FINDSITE comb2.0 represents a significant improvement in the state-of-the-art. The FINDSITE comb2.0 web service is freely available for academic users at http://pwp.gatech.edu/cssb/FINDSITE-COMB-2 .