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

Lesley Ann Howell, Andrew Michael Beekman

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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.
Original languageEnglish
Pages (from-to)215-219
Number of pages5
JournalRSC Chemical Biology
Volume2
Issue number1
Early online date19 Nov 2020
DOIs
Publication statusPublished - 1 Feb 2021

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