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Structure-based computational methods have contributed to recent successes in the development of small molecules to study GPCR function and to act as therapeutics, including the identification of new ligands for orphan GPCRs, allosteric regulators, and biased ligands.
Allosteric modulation and biased agonism at GPCRs could be manifestations of the same underlying 'conformational selection' mechanism, and these can be harmonized by considering the influence of ligand–receptor residence time and kinetic context.
The organelles and subcellular compartments of yeast provide distinct environments and physical separation from the cytosol, enabling opportunities to target biosynthetic pathways to these compartments and enhance production of desirable compounds.
A variety of chemical and enzymatic techniques, each with their own considerations for use, have been developed for the site-selective bioconjugation of desirable moieties to proteins via the unique handle of the N terminus.
Recent advances in metabolic engineering provide possible new approaches for the production of advanced intermediates as tractable semisynthetic starting materials for alkaloid-derived pharmaceuticals and potential new drugs.
This perspective discusses recent progress in the development of pharmacological tools that initiate mitophagy and spare mitochondrial function and focuses on promising approaches to identify improved reagents.