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Updated: May 1, 2026

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
Published on: May 20, 2020
Computational design of binding proteins to EGFR domain II
Yoon Sup Choi1, Soomin Yoon2, Kyung-Lock Kim3
1Cancer Research Institute, Seoul National University School of Medicine, Seoul, Republic of Korea; School of Interdisciplinary Bioscience and Bioengineering (I-Bio), Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea; KT Institute of Convergence Technology, Seocho-gu, Seoul, Korea.
Abstract:
We developed a process to produce novel interactions between two previously unrelated proteins. This process selects protein scaffolds and designs protein interfaces that bind to a surface patch of interest on a target protein. Scaffolds with shapes complementary to the target surface patch were screened using an exhaustive computational search of the human proteome and optimized by directed evolution using phage display. This method was applied to successfully design scaffolds that bind to epidermal growth factor receptor (EGFR) domain II, the interface of EGFR dimerization, with high reactivity toward the target surface patch of EGFR domain II. One potential application of these tailor-made protein interactions is the development of therapeutic agents against specific protein targets.
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