In-silico investigation of the ErbB family dimerization mechanism

The human epidermal growth factor receptor family contains four distinct receptors, including ErbB1, ErbB2, ErbB3, and ErbB4. These receptors are the key players of cell signaling in tumor development and function in heterodimer or homodimer forms. This study explores the ErbB hetero and homodimers’ potential in constructing the active back-to-back dimer using molecular modeling and molecular docking techniques. Among the modeled dimers, 21 out of 37 back-to-back ones were heterodimers. Suggesting that heterodimerization is the dominant active form of the ErbB receptors. Docking results show that ErbB1-ErbB1, ErbB1-ErbB4, and ErbB2-ErbB3 dimers are the most favorable dimeric structures. These findings are crucial in defining novel epitopes for therapeutic anti-cancer designs against ErbB receptors.