An open-source drug discovery platform enables ultra-large virtual screens
We are delighted to announce another application of Enamine REAL database recently published in Nature. This paper is a result of the collaborative effort of scientists from Enamine and the leading academic institutions from the USA and Germany.
The paper describes an application of VirtualFlow, a highly automated open-source platform able to prepare and efficiently screen ultra-large ligand libraries. Using VirtualFlow, we have prepared the largest ready-to-dock ligand library available to date, with over 1.4 billion commercially available molecules mostly based on the REAL database. To demonstrate the power of VirtualFlow, we screened over 1 billion compounds and discovered a small molecule inhibitor (iKeap1) that engages KEAP1 with nanomolar affinity (Kd = 114 nM) and disrupts the interaction between KEAP1 and the transcription factor NRF2. We also identified a set of structurally diverse molecules that bind to KEAP1 with submicromolar affinity. This illustrates the potential of VirtualFlow to access vast regions of the chemical space and of the REAL database to provide starting points from the initial hit finding.