At LifeArc we have established a high-throughput protein workflow to advance early-stage small molecule drug discovery projects from target and construct selection through to high-throughput fragment screening by SPR and ligandability assessment. Antimicrobial drug resistance is a public health crisis facing the world, and novel antimicrobial therapies are required to help address this challenge. We have applied our workflow to early-stage antimicrobial drug discovery work, progressing from lists of essential genes to structurally enabled validated hits ready for medicinal chemistry progression. This involved using high-throughput approaches to efficiently generate and test multiple protein constructs in parallel. Collecting protein QC data and large amounts of fragment binding data allowed us to compare target proteins, empowering decision making and providing starting points for fragment-based drug discovery. Analysis of the resulting data allows us to prioritise target proteins and constructs which are scaled up for use in biochemical and biophysical assays as well as structural biology. Although we have applied this workflow to the area of antimicrobials, it could be applied to any drug design project where multiple potential targets could be addressed in parallel.
