Investigation of Muscarinic Acetylcholine Receptor M Activation in Atomistic Detail: A Chemist's Viewpoint.

We analyzed the precise ligand:receptor interactions required for activation of the muscarinic acetylcholine receptor M, a prototypical G protein-coupled receptor and potential diabetes target. Starting from literature-known compounds and docking solutions, ligands were tailored for the modulation of this receptor's activation. Several aspects of the structure-activity relationship of agonists were investigated in atomistic detail, in order to delineate how the receptor can be activated via the orthosteric site.

RNase P Inhibitors Identified as Aggregators.

RNase P is an essential enzyme responsible for tRNA 5'-end maturation. In most bacteria, the enzyme is a ribonucleoprotein consisting of a catalytic RNA subunit and a small protein cofactor termed RnpA. Several studies have reported small-molecule inhibitors directed against bacterial RNase P that were identified by high-throughput screenings.