Describe high-throughput screening (HTS) approaches in drug discovery.

High-throughput screening rapidly tests large compound libraries against biological targets. Components: 1) Assay development - biochemical assays (enzyme inhibition, binding), cell-based assays (reporter genes, phenotypic), or biophysical methods (SPR, thermal shift). 2) Assay miniaturization - 384 or 1536-well plates reduce reagent use and increase throughput. 3) Automation - robotic liquid handlers, plate readers, stackers enable thousands of tests per day. 4) Compound libraries - diversity libraries, fragment libraries, natural products, or focused sets. 5) Data analysis - identify hits above threshold, Z-factor quality metric, dose-response confirmation. 6) Hit validation - confirm hits in orthogonal assays, assess selectivity, eliminate artifacts (fluorescence interference, compound reactivity). Virtual/in silico screening computationally prioritizes compounds before testing. Fragment-based screening identifies small molecules for fragment-growing optimization.