Anatomy of fingerprint search calculations on structurally diverse sets of active compounds

Similarity searching using molecular fingerprints is a widely used approach for the identification of novel hits. A fingerprint search involves many pairwise comparisons of bit string representations of known active molecules with those precomputed for database compounds. Bit string overlap, as evaluated by various similarity metrics, is used as a measure of molecular similarity. Results of a number of studies focusing on fingerprints suggest that it is difficult, if not impossible, to develop generally applicable search parameters and strategies, irrespective of the compound classes under investigation. Rather, more or less, each individual search problem requires an adjustment of calculation conditions. Thus, there is a need for diagnostic tools to analyze fingerprint-based similarity searching. We report an analysis of fingerprint search calculations on different sets of structurally diverse active compounds. Calculations on five biological activity classes were carried out with two fingerprints in two compound source databases, and the results were analyzed in histograms. Tanimoto coefficient (Tc) value ranges where active compounds were detected were compared to the distribution of Tc values in the database. The analysis revealed that compound class-specific effects strongly influenced the outcome of these fingerprint calculations. Among the five diverse compound sets studied, very different search results were obtained. The analysis described here can be applied to determine Tc intervals where scaffold hopping occurs. It can also be used to benchmark fingerprint calculations or estimate their probability of success.     

Relationship between wine scores and visible–near-infrared spectra of Australian red wines

Sensory analysis of wine involves the measurement, interpretation and understanding of human responses to the properties perceived by the senses such as sight, smell and taste. The sensory evaluation of wine is often carried out by wine judges, winemakers and technical staff, and allows characterization of the quality of the wine. However, this method is lengthy, expensive, and its results depend on panel training and the specific vocabulary used by the panel. A robust, rapid, unbiased and inexpensive method to assist in quality assessment purposes will therefore be beneficial for the modern wine industry. This study aims to investigate the relationship between sensory analysis, visible (VIS) and near-infrared (NIR) spectroscopy to assess sensory properties of commercial Australian wine varieties. For the purposes of this study 118 red wine samples (Cabernet Sauvignon, Shiraz, Pinot Noir, Tempranillo, Nebbiolo and blends) graded by a panel of experienced tasters and scored according to the Australian wine show system were scanned in transmission in the VIS and NIR range (400–2,500nm). Partial least squares regression models were developed between the overall score given by the judges and the combined VIS–NIR spectra, using full cross validation (leave-one-out method). The results showed that NIR spectroscopy was able to predict wine quality scores in red wine samples (R = 0.61 and standard error of prediction of 0.81). The practical implication of this study is that instrumental methods such as VIS–NIR spectroscopy can be used to complement sensory analysis and can facilitate the task at early stages of product development, making high-throughput screening of novel products feasible or maintaining the consistency of the product.     

Eine Methode zur Bestimmung von Natrium, Kalium und Chlor in Nahrungsmitteln

Ohne Zusammenfassung     

Electron spin density distribution in the polymer phase of CsC60: assignment of the NMR spectrum

We present high resolution 133Cs-13C double resonance NMR data and 13C-13C NMR correlation spectra of 13C enriched samples of the polymeric phase of CsC60. These data lead to a partial assignment of the lines in the 13C NMR spectrum of CsC60 to the carbon positions on the C60 molecule. A plausible completion of the assignment can be made on the basis of an ab initio calculation. The data support the view that the conduction electron density is concentrated at the C60 "equator," away from the interfullerene bonds.     

A distance function for retrieval of active molecules from complex chemical space representations

The concept of chemical space is of fundamental importance for chemoinformatics research. It is generally thought that high-dimensional space representations are too complex for the successful application of many compound classification or virtual screening methods. Here, we show that a simple "activity-centered" distance function is capable of accurately detecting molecular similarity relationships in "raw" chemical spaces of high dimensionality.