In silico peptide-directed ligand design complements experimental peptide-directed binding for protein–protein interaction modulator discovery

Howell, Lesley Ann and Beekman, Andrew Michael (2021) In silico peptide-directed ligand design complements experimental peptide-directed binding for protein–protein interaction modulator discovery. RSC Chemical Biology, 2 (1). pp. 215-219. ISSN 2633-0679

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Abstract

Using the protein–protein interaction of Mcl-1/Noxa, two methods for efficient modulator discovery are directly compared. In silico peptide-directed ligand design is evaluated against experimental peptide-directed binding, allowing for the discovery of two new inhibitors of Mcl-1/Noxa with cellular activity. In silico peptide-directed ligand design demonstrates an in vitro hit rate of 80% (IC50 < 100 μM). The two rapid and efficient methods demonstrate complementary features for protein–protein interaction modulator discovery.

Item Type:	Article
Additional Information:	Funding Information: This work was funded in part through a Royal Society Research Grant RGS/R1/201008 and EPSRC New Investigator Grant EP/ M006379/1. We acknowledge the EPSRC UK National Mass Spectrometry Facility at Swansea University.
Uncontrolled Keywords:	biochemistry,molecular biology,biochemistry, genetics and molecular biology (miscellaneous),chemistry (miscellaneous) ,/dk/atira/pure/subjectarea/asjc/1300/1303
Faculty \ School:	Faculty of Science > School of Pharmacy (former - to 2024)
UEA Research Groups:	Faculty of Science > Research Groups > Chemical Biology and Medicinal Chemistry (former - to 2021)
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	20 Nov 2020 00:53
Last Modified:	01 May 2025 00:03
URI:	https://ueaeprints.uea.ac.uk/id/eprint/77738
DOI:	10.1039/D0CB00148A

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