Biophysical Techniques

Biophysical approaches are used to determine how two or more molecules, such as two proteins or a protein and a small molecule, bond together. These strategies have become more widely employed in small molecule discovery during the last 20 years, from screening to lead optimization. Biophysical approaches can distinguish drug-like binding (1:1 binding between a tiny molecule and a protein site) from artifactual inhibitory mechanisms such as aggregation by assessing binding rather than protein function. High-throughput, compact test formats, as well as the availability of low-cost automation, have fueled recent improvements in biophysical approaches for screening. Collaborative initiatives have made traditionally low-throughput, high-resolution structure-based technologies broadly available. Biophysical approaches are employed in various stages of the drug development process, including searching for new receptor ligands, determining pharmacological mechanisms, and confirming findings from biochemical and cellular experiments.