Computational Design of Fusion Proteins Against ErbB2-amplified Tumors Inspired by Ricin Toxin

Overview

Journal Front Mol Biosci

Specialty Biology

Date 2023 Mar 20

PMID 36936983

Authors

Yasser Ahmadi Moghaddam

Asad Maroufi

Sara Zareei

Mehdi Irani

Affiliations

Soon will be listed here.

Abstract

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.

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