9th Fragment-based Drug Discovery Meeting

Schrödinger is excited to be participating in the 9th Fragment-based Drug Discovery Meeting taking place on March 3rd – 5th in Cambridge, United Kingdom at Hinxton Hall. Join us for a poster by Antonija Kuzmanic, Principal Scientist I at Schrödinger, titled “Large-scale in silico Fragment Screening Based on Absolute Free Energy Perturbation (AB-FEP+).”

Title: Large-scale in silico Fragment Screening Based on Absolute Free Energy Perturbation (AB-FEP+)
Speaker: Antonija Kuzmanic, Principal Scientist I
Abstract: Fragment screening has witnessed remarkable success with 6 FDA approved drugs and many more in clinical trials. Here we present a computational innovation to dramatically expand the scope of fragment screening, from screening typical ~3k – 30k experimental fragment libraries to screening ~200 million fragments with high hit rates. This approach involves a virtual screening funnel based on Absolute Free Energy Perturbation to rigorously score diverse fragments based on their predicted binding affinities, allowing for only a small number of fragments (~25-50) to be purchased and/or synthesized for experimental testing. This approach has already been successfully applied during the hit finding stage for several active internal drug discovery projects, resulting in potent (nM – uM), ligand efficient (LE 0.38 – 0.51) starting points from which to initiate our discovery campaigns. In the TPL2 project, five fragments hits (<100 uM) were identified from fragment screening and were expanded to develop initial SAR, which led to discovery of the hit compounds.