2017, 57, 529-539). For commercial algorithms, the median minimum root-mean-square deviations measured between protein-bound ligand conformations and ensembles of a maximum of 250 conformers are between 0.46 and 0.61 Å. Commercial conformer ensemble generators are characterized by their high robustness, with at least 99% of all input molecules successfully processed and few or even no substantial geometrical errors detectable in their output conformations. The RDKit distance geometry algorithm (with minimization enabled) appears to be a good free alternative since its performance is comparable to that of the midranked commercial algorithms. Based on a statistical analysis, we elaborate on which algorithms to use and how to parametrize them for best performance in different application scenarios.

We developed a cheminformatics pipeline for the fully automated selection and extraction of high-quality protein-bound ligand conformations from X-ray structural data. The pipeline evaluates the validity and accuracy of the 3D structures of small molecules according to multiple criteria, including their fit to the electron density and their physicochemical and structural properties. Using this approach, we compiled two high-quality datasets from the Protein Data Bank (PDB): a comprehensive dataset and a diversified subset of 4626 and 2912 structures, respectively. The datasets were applied to benchmarking seven freely available conformer ensemble generators: Balloon (two different algorithms), the RDKit standard conformer ensemble generator, the Experimental-Torsion basic Knowledge Distance Geometry (ETKDG) algorithm, Confab, Frog2 and Multiconf-DOCK. Substantial differences in the performance of the individual algorithms were observed, with RDKit and ETKDG generally achieving a favorable balance of accuracy, ensemble size and runtime. The Platinum datasets are available for download from http://www.zbh.uni-hamburg.de/platinum_dataset .

The opportunity to work at any time and place, which is facilitated by mobile communication technologies, reinforces employer expectations that employees are available for work beyond regular work hours. This study investigates the relation of daily extended work availability with psychological and physiological well-being and the mediating role of recovery experiences. We hypothesized that recovery is limited under conditions of extended work availability, which may impair well-being. A sample of 132 individuals from 13 organizations provided daily survey measures over a period of 4 days during which they were required to be available during nonworking hours and 4 days during which they were not required to be available. A subsample of 51 persons provided morning cortisol levels in addition to the survey data. The analysis of within-person processes using multilevel structural equation modeling revealed significant effects of extended work availability on the daily start-of-day mood and cortisol awakening response. Mediation analysis revealed that the recovery experience of control over off-job activities mediated the observed relationship with start-of-day mood but not the relationship with the cortisol awakening response. The results demonstrate that nonwork hours during which employees are required to remain available for work cannot be considered leisure time because employees’ control over their activities is constrained and their recovery from work is restricted.

Computer-aided drug design methods such as docking, pharmacophore searching, 3D database searching, and the creation of 3D-QSAR models need conformational ensembles to handle the flexibility of small molecules. Here, we present Conformator, an accurate and effective knowledgebased algorithm for generating conformer ensembles. With 99.9% of all test molecules processed, Conformator stands out by its robustness with respect to input formats, molecular geometries, and the handling of macrocycles. With an extended set of rules for sampling torsion angles, a novel algorithm for macrocycle conformer generation, and a new clustering algorithm for the assembly of conformer ensembles, Conformator reaches a median minimum root-mean-square deviation (measured between protein-bound ligand conformations and ensembles of a maximum of 250 conformers) of 0.47 Å with no significant difference to the highest-ranked commercial algorithm OMEGA and significantly higher accuracy than seven free algorithms, including the RDKit DG algorithm. Conformator is freely available for noncommercial use and academic research.

The present study reports the lagged effects of work stress on work-related rumination, restful sleep, and nocturnal heart rate variability experienced during both workdays and weekends. Fifty employees participated in a diary study. Multilevel and regression analyses revealed a significant relationship between work stress measured at the end of a workday, work-related rumination measured during the evening, and restful sleep measured the following morning. Work stress, measured as the mean of 2 consecutive workdays, was substantially but not significantly related to restful sleep on weekends. Work stress was unrelated to nocturnal heart rate variability. Work-related rumination was related to restful sleep on weekends but not on workdays. Additionally, work-related rumination on weekends was positively related to nocturnal heart rate variability during the night between Saturday and Sunday. No mediation effects of work stress on restful sleep or nocturnal heart rate variability via work-related rumination were confirmed.