Computational design of fusion proteins against ErbB2-amplified tumors inspired by ricin toxin

Although the anti-cancer activity of ricin is well-known, its non-specific targeting challenges the development of ricin-derived medicines. In the present study, novel potential ribosome-inactivating fusion proteins (RIPs) were computationally engineered by incorporation of an ErbB2-dependant penetr...

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Bibliographic Details
Published in:Frontiers in molecular biosciences 2023-03, Vol.10, p.1098365-1098365
Main Authors: Ahmadi Moghaddam, Yasser, Maroufi, Asad, Zareei, Sara, Irani, Mehdi
Format: Article
Language:English
Subjects:
cancer
chimeric protein
ErbB2
Molecular Biosciences
molecular dynamics
ricin
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Summary:Although the anti-cancer activity of ricin is well-known, its non-specific targeting challenges the development of ricin-derived medicines. In the present study, novel potential ribosome-inactivating fusion proteins (RIPs) were computationally engineered by incorporation of an ErbB2-dependant penetrating peptide (KCCYSL, MARAKE, WYSWLL, MARSGL, MSRTMS, and WYAWML), a linker (either EAAAK or GGGGS) and chain A of ricin which is responsible for the ribosome inactivation. Molecular dynamics simulations assisted in making sure that the least change is made in conformation and dynamic behavior of ricin chain A in selected chimeric protein (CP). Moreover, the potential affinity of the selected CPs against the ligand-uptaking ErbB2 domain was explored by molecular docking. The results showed that two CPs (CP2 and 10) could bind the receptor with the greatest affinity.
ISSN:2296-889X
2296-889X
DOI:10.3389/fmolb.2023.1098365