Accelerating BRPF1b hit identification with BioPhysical and Active Learning Screening (<i>BioP</i>ALS)-Reference-Cited by-同舟云学术

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

Published:2024-03 Issue:6 Volume:19 Page:
ISSN:1860-7179
Container-title:ChemMedChem
language:en
Short-container-title:ChemMedChem

Author:

Pal Sandeep¹,Nare Zandile¹^ORCID,Rao Vincenzo A.¹^ORCID,Smith Brian O.²^ORCID,Morrison Ian¹,Fitzgerald Edward A.³^ORCID,Scott Andrew¹,Bingham Matilda J.¹,Pesnot Thomas¹^ORCID

Affiliation:

1. Concept Life Sciences Frith Knoll Road, Chapel-en-le-Frith SK23 0PG High Peak UK

2. University of Glasgow School of Molecular Biosciences College of Medical Veterinary and Life Sciences G12 8QQ Glasgow UK

3. Malvern Panalytical Zugerstrasse 76 CH-8820 Wädenswil Switzerland

Abstract

AbstractWe 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 properties. In addition to the excellent in silico/in vitro confirmation rate demonstrated with BRPF1b, binding kinetics were determined, and binding topologies predicted for all hits. BioPALS is a lean, data‐rich, and standardized approach to hit identification applicable to a wide range of biological targets.

Publisher

Wiley

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