How accurate do structures of the β 2 adrenergic receptor (β 2 AR) need to be to effectively serve as platforms for docking-based virtual screening campaigns? To answer this research question, here we targeted through controlled virtual screening experiments 23 homology models of the β 2 AR endowed with different levels of structural accuracy. Subsequently, we studied the correlation between virtual screening performance and structural accuracy of the targeted models. Moreover, we studied the correlation between virtual screening performance and template/target receptor sequence identity. Our study demonstrates that docking-based virtual screening campaigns targeting homology models of the β 2 AR, in the majority of the cases, yielded results that exceeded random expectations in terms of area under the receiver operating characteristic curve (ROC AUC). Moreover, with the most effective scoring method, over one third and one quarter of the models yielded results that exceeded random expectation also in terms of enrichment factors (EF1, EF5, and EF10) and BEDROC (α = 160.9), respectively. Not surprisingly, we found a detectable linear correlation between virtual screening performance and structural accuracy of the ligandbinding cavity. We also found a detectable linear correlation between virtual screening performance and structural accuracy of the second extracellular loop (EL2). Finally, our data indicate that, although there is no detectable linear correlation between virtual screening performance and template/β 2 AR sequence identity, models built on the basis of templates that show high sequence identity with the β 2 AR, especially within the ligand-biding cavity, performed consistently well. Conversely, models with lower sequence identity displayed performance levels

Cellular heterogeneity is an inherent property of cell populations with a wide spectrum of biological manifestations, ranging from barely observable variations that enhance organismal adaptation, to life‐threatening differences. Single‐cell metabolomics can reveal molecular information and variations in metabolite concentrations between cells that are masked in cell‐population studies. These differences are quantitatively captured by the abundance distributions for the population and their statistical analysis can reveal the presence of latent subpopulations. In recent years, mass spectrometry (MS), combined with novel sampling and ionization techniques, has become an important tool for single‐cell metabolomics. These new techniques must contend with significant challenges in the form of small cell sizes and volumes, ultratrace metabolite amounts per cell, and potentially interfering high turnover rates and rapid diffusion. Owing to the ultrasmall sample volume, low abundance of some metabolites, and poor ionization efficiencies, metabolite detection, identification, and accurate quantitation remain a major challenge. The ability of some techniques to analyze tissue‐embedded cells opens the door for spatial metabolomics, potentially revealing cellular synergism in organ level metabolism. In this Concept article, we present a bird's eye view of these major themes in single cell metabolomics and some of the relevant MS‐based methods.

Laser ablation electrospray ionization (LAESI) driven by mid-infrared laser pulses, allows the direct analysis of biological tissues with minimal sample preparation. Dedicated remote ablation chambers have been developed to eliminate...