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Publication Abstract from PubMed

Understanding the relationship between protein sequence and structure well enough to design new proteins with desired functions is a longstanding goal in protein science. Here, we show that recurring tertiary structural motifs (TERMs) in the PDB provide rich information for protein-peptide interaction prediction and design. TERM statistics can be used to predict peptide binding energies for Bcl-2 family proteins as accurately as widely used structure-based tools. Furthermore, design using TERM energies (dTERMen) rapidly and reliably generates high-affinity peptide binders of anti-apoptotic proteins Bfl-1 and Mcl-1 with just 15%-38% sequence identity to any known native Bcl-2 family protein ligand. High-resolution structures of four designed peptides bound to their targets provide opportunities to analyze the strengths and limitations of the computational design method. Our results support dTERMen as a powerful approach that can complement existing tools for protein engineering.

Tertiary Structural Motif Sequence Statistics Enable Facile Prediction and Design of Peptides that Bind Anti-apoptotic Bfl-1 and Mcl-1.,Frappier V, Jenson JM, Zhou J, Grigoryan G, Keating AE Structure. 2019 Feb 12. pii: S0969-2126(19)30008-5. doi:, 10.1016/j.str.2019.01.008. PMID:30773399^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.