Accelerating BRPF1b hit identification with BioPhysical and Active Learning Screening (BioPALS)

Pal, S., Nare, Z., Rao, V. A., Smith, B. O. , Morrison, I., Fitzgerald, E. A., Scott, A., Bingham, M. J. and Pesnot, T. (2024) Accelerating BRPF1b hit identification with BioPhysical and Active Learning Screening (BioPALS). ChemMedChem, 19(6), e202300590. (doi: 10.1002/cmdc.202300590) (PMID:38372199)

Abstract

We report the development of BioPhysical and Active Learning Screening (BioPALS); a rapid and versatile hit identification protocol combining AI‐powered virtual screening with a GCI‐driven biophysical confirmation workflow. Its application to the BRPF1b bromodomain afforded a range of novel micromolar binders with favorable ADMET parameters. In addition to the excellent in silico/in vitro confirmation rate demonstrated with BRPF1b, binding kinetics are determined, and binding topologies predicted for all hits. BioPALS is a lean, data‐rich, and standardized approach to hit identification applicable to wide range of biological targets.

• Item Type: Articles
• Keywords: Hit identification, virtual screening, machine learning, BRPF1, grating coupled interferometry.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Smith, Dr Brian
• Authors: Pal, S., Nare, Z., Rao, V. A., Smith, B. O., Morrison, I., Fitzgerald, E. A., Scott, A., Bingham, M. J., and Pesnot, T.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: ChemMedChem
• Publisher: Wiley
• ISSN: 1860-7179
• ISSN (Online): 1860-7187
• Published Online: 19 February 2024
• Copyright Holders: Copyright © 2024 Chemistry Europe and Wiley-VCH GmbH
• First Published: First published in ChemMedChem 19(6):e202300590
• Publisher Policy: Reproduced in accordance with the publisher copyright policy