A virtual library of small molecules mimicking dipeptides.

Virtual combinatorial libraries are prevalent in drug discovery due to improvements in the prediction of synthetic reactions that can be performed. This has gone hand in hand with the development of virtual screening capabilities to effectively screen the large chemical spaces spanned by exhaustive enumeration of reaction products. In this study, we generated a small-molecule dipeptide mimic library to target proteins binding small peptides.

Differential interaction patterns of opioid analgesics with µ opioid receptors correlate with ligand-specific voltage sensitivity.

The µ opioid receptor (MOR) is the key target for analgesia, but the application of opioids is accompanied by several issues. There is a wide range of opioid analgesics, differing in their chemical structure and their properties of receptor activation and subsequent effects. A better understanding of ligand-receptor interactions and the resulting effects is important.

How Carvedilol activates β-adrenoceptors.

Carvedilol is among the most effective β-blockers for improving survival after myocardial infarction. Yet the mechanisms by which carvedilol achieves this superior clinical profile are still unclear. Beyond blockade of β-adrenoceptors, arrestin-biased signalling via β-adrenoceptors is a molecular mechanism proposed to explain the survival benefits.

The Isoleucine at Position 118 in Transmembrane 2 Is Responsible for the Selectivity of Xamoterol, Nebivolol, and ICI89406 for the Human 1-Adrenoceptor.

Known off-target interactions frequently cause predictable drug side-effects (e.g., 1-antagonists used for heart disease, risk 2-mediated bronchospasm).

Association of variants with hemoglobin A1c and impact on diabetes diagnosis in East Asian individuals.

Objective: Hemoglobin A1c (HbA1c) accuracy is important for diabetes diagnosis and estimation of overall glycemia. The Asahi variant which causes glucose-6-phosphate dehydrogenase (G6PD) deficiency has been shown to lower HbA1c independently of glycemia in African ancestry populations. As different variants occur in Asian ancestry, we sought to identify Asian-specific variants associated with HbA1c.

A benchmarking study on virtual ligand screening against homology models of human GPCRs.

G-protein-coupled receptor (GPCR) is an important target class of proteins for drug discovery, with over 27% of FDA-approved drugs targeting GPCRs. However, being a membrane protein, it is difficult to obtain the 3D crystal structures of GPCRs for virtual screening of ligands by molecular docking. Thus, we evaluated the virtual screening performance of homology models of human GPCRs with respect to the corresponding crystal structures.