Ligand-receptor interaction platforms and their applications for drug discovery

The study of drug-target interactions is essential for the understanding of biological processes and for the efforts to develop new therapeutic molecules. Increased ligand-binding assays have coincided with the advances in reagents, detection and instrumentation technologies, the expansion in therapeutic targets of interest, and the increasingly recognized importance of biochemical aspects of drug-target interactions in determining the clinical performance of drug molecules. Nowadays, ligand-binding assays can determine every aspect of many drug-target interactions.

Given that ligand-target interactions are very diverse, the author has decided to focus on the binding of small molecules to protein targets. This article first reviews the key biochemical aspects of drug-target interactions, and then discusses the detection principles of various ligand-binding techniques in the context of their primary applications for drug discovery and development.

Equilibrium-binding affinity should not be used as a solo indicator for the in vivo pharmacology of drugs. The clinical relevance of drug-binding kinetics demands high throughput kinetics early in drug discovery. The dependence of ligand binding and function on the conformation of targets necessitates solution-based and whole cell-based ligand-binding assays. The increasing need to examine ligand binding at the proteome level, driven by the clinical importance of the polypharmacology of ligands, has started to make the structure-based in silico binding screen an indispensable technique for drug discovery and development. Integration of different ligand-binding assays is important to improve the efficiency of the drug discovery and development process.