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Separate Test Set (separate + test_set)
Selected AbstractsH-bond donor strength;JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 9 2009Abraham parameter; A quantum chemical model is introduced to predict the H-bond donor strength of monofunctional organic compounds from their ground-state electronic properties. The model covers OH, NH, and CH as H-bond donor sites and was calibrated with experimental values for the Abraham H-bond donor strength parameter A using the ab initio and density functional theory levels HF/6-31G** and B3LYP/6-31G**. Starting with the Morokuma analysis of hydrogen bonding, the electrostatic (ES), polarizability (PL), and charge transfer (CT) components were quantified employing local molecular parameters. With hydrogen net atomic charges calculated from both natural population analysis and the ES potential scheme, the ES term turned out to provide only marginal contributions to the Abraham parameter A, except for weak hydrogen bonds associated with acidic CH sites. Accordingly, A is governed by PL and CT contributions. The PL component was characterized through a new measure of the local molecular hardness at hydrogen, ,(H), which in turn was quantified through empirically defined site-specific effective donor and acceptor energies, EEocc and EEvac. The latter parameter was also used to address the CT contribution to A. With an initial training set of 77 compounds, HF/6-31G** yielded a squared correlation coefficient, r2, of 0.91. Essentially identical statistics were achieved for a separate test set of 429 compounds and for the recalibrated model when using all 506 compounds. B3LYP/6-31G** yielded slightly inferior statistics. The discussion includes subset statistics for compounds containing OH, NH, and active CH sites and a nonlinear model extension with slightly improved statistics (r2 = 0.92). © 2008 Wiley Periodicals, Inc. J Comput Chem 2009 [source] Development of a New Pharmacophore Model That Discriminates Active Compstatin AnalogsCHEMICAL BIOLOGY & DRUG DESIGN, Issue 4 2008Ting-Lan Chiu Compstatin and its active peptide analogs can potentially be used for therapeutic purposes because their binding to the third component of complement prohibits its conversion into the proteolytically activated form of the third component of complement, thus inhibiting complement cascades in all three complement pathways. Mallik and Morikis built three quasi-dynamic pharmacophore models for compstatin peptide analogs before, but only nine compstatin peptide analogs were incorporated in their study and the most active compstatin analog had only medium inhibitory activity. Since then, many more compstatin analogs have been synthesized and their inhibitory activities tested. Furthermore, the X-ray structure of AcCompNH2-V4W-H9A bound to the third component of complement has become available (PDB ID: 2QKI). In this paper, we utilized all the new information and built a new pharmacophore model using a distinct approach. Our model demonstrated good performance in a separate test set of 82 compstatin analogs: it accurately identified 70% of the analogs of medium or high inhibitory activities and misclassified only 8.5% of the analogs of low or no inhibitory activities. The results proved our pharmacophore model to be a filter of great sensitivity and specificity. [source] Human skin permeation and partition: General linear free-energy relationship analysesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 6 2004Michael H. Abraham Abstract Literature values of the permeability coefficient for permeation of human skin from water have been adjusted for ionization in water and adjusted for temperature. The obtained values of log Kp for 119 solutes at 37°C have been correlated with Abraham descriptors to yield an equation with R2,=,0.832 and SD,=,0.46 log units. Three separate test sets of 60 compounds had log Kp predicted with an SD of 0.48 log units. The main factors that influence log Kp are solute hydrogen bond basicity that lowers the permeability coefficient and solute volume that increases the permeability coefficient. Human skin,water partition coefficients, as log Ksc, have been collected for 45 compounds and yield an equation with R2,=,0.926 and SD,=,0.22 log units. We have compared the log Kp equation to equations for various other processes, but have found no process that appears to be similar to that for skin permeation. The nearest process to skin,water partition is the isobutanol,water partition system. An equation for lateral diffusion in the stratum corneum is shown to be reasonably close to various diffusion-related processes. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1508,1523, 2004 [source] Patient gender and radiopharmaceutical tracer is of minor importance for the interpretation of myocardial perfusion images using an artificial neural networkCLINICAL PHYSIOLOGY AND FUNCTIONAL IMAGING, Issue 3 2006Kristina Tägil Summary The purpose of this study was to assess the influence of patient gender and choice of perfusion tracer on computer-based interpretation of myocardial perfusion images. For the image interpretation, an automated method was used based on image processing and artificial neural network techniques. A total of 1000 patients were studied, all referred to the Royal Brompton Hospital in London for myocardial perfusion scintigraphy over a period of 1 year. The patients were randomized to receive either thallium or one of the two technetium tracers, methoxyisobutylisonitrile or tetrofosmin. Artificial neural networks were trained with either mixed gender or gender-specific and mixed tracer or tracer-specific training sets of different sizes. The performance of the networks was assessed in separate test sets, with the interpretation of experienced physicians regarding the presence or absence of fixed or reversible defects in the images as the gold standard. The neural networks trained with large mixed gender training sets were as good as the networks trained with gender-specific data sets. In addition, the neural networks trained with large mixed tracer training sets were as good as or better than the networks trained with tracer-specific data sets. Our results indicate that the influence of patient gender and perfusion tracer are of minor importance for the computer-based interpretation of the myocardial perfusion images. The differences that occur can be compensated for by larger training sets. [source] | ||||||||||