Funneling modulatory peptide design with generative models: Discovery and characterization of disruptors of calcineurin protein-protein interactions
Fig 2
Overview of the protocol for design of peptide inhibitors of a target PPI.
The protein substrates of the target enzyme are first identified from previous experiments together with their binding fragment. Additional interacting orthologs are identified by homology search, and the corresponding binding regions are extracted and aligned. A sequence generative model (SGM) is trained to generate a library of candidate peptides. The latter are screened for affinity by structural modeling and high-throughput binding assay. The best candidates are selected for further low-throughput experimental characterization.