Investigation of the interactions between the EphB2 receptor and SNEW peptide variants

Buyong Ma*, Stephanie Kolb, Michael Diprima, Molleshree Karna, Giovanna Tosato, Qiqi Yang, Qiang Huang, Ruth Nussinov

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


EphB2 interacts with cell surface-bound ephrin ligands to relay bidirectional signals. Overexpression of the EphB2 receptor protein has been linked to different types of cancer. The SNEW (SNEWIQPRLPQH) peptide binds with high selectivity and moderate affinity to EphB2, inhibiting Eph-ephrin interactions by competing with ephrin ligands for the EphB2 high-affinity pocket. We used rigorous free energy perturbation (FEP) calculations to re-evaluate the binding interactions of SNEW peptide with the EphB2 receptor, followed by experimental testing of the computational results. Our results provide insight into dynamic interactions of EphB2 with SNEW peptide. While the first four residues of the SNEW peptide are already highly optimized, change of the C-terminal end of the peptide has the potential to improve SNEW-binding affinity. We identified a PXSPY motif that can be similarly aligned with several other EphB2-binding peptides.

Original languageEnglish
Pages (from-to)236-246
Number of pages11
JournalGrowth Factors
Issue number6
StatePublished - 1 Dec 2014


FundersFunder number
National Institutes of HealthHHSN261200800001E
National Institutes of Health
National Cancer InstituteZIABC010782
National Cancer Institute
National Institute of Biomedical Imaging and Bioengineering
Natural Science Foundation of Shanghai13ZR1402400
Natural Science Foundation of Shanghai
Council for Chemical Research
Shanghai Leading Academic Discipline ProjectB111
Shanghai Leading Academic Discipline Project
National High-tech Research and Development Program2008AA02Z311
National High-tech Research and Development Program


    • EphB2 receptor
    • Ephrin ligands
    • Inhibitor design
    • Molecular dynamics simulations
    • Protein dynamics
    • Protein stability


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