Computational design of binding proteins to EGFR domain II.
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.
Cancer 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.
Yoon Sup
YS
Choi
Cancer Research Institute, Seoul National University School of Medicine, Seoul, Republic of Korea; Department of Biochemistry and Molecular Biology, Seoul National University School of Medicine, Seoul, Republic of Korea.
Soomin
S
Yoon
Division of Integrative Bioscience and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
Kyung-Lock
KL
Kim
Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
Jiho
J
Yoo
Division of Integrative Bioscience and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
Parkyong
P
Song
Cancer Research Institute, Seoul National University School of Medicine, Seoul, Republic of Korea; Scripps Korea Antibody Institute, Chuncheon, Republic of Korea.
Minsoo
M
Kim
Division of Integrative Bioscience and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
Young-Eun
YE
Shin
Cancer Research Institute, Seoul National University School of Medicine, Seoul, Republic of Korea; Department of Biochemistry and Molecular Biology, Seoul National University School of Medicine, Seoul, Republic of Korea.
Won Jun
WJ
Yang
Division of Integrative Bioscience and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
Jung-eun
JE
Noh
Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
Hyun-Soo
HS
Cho
School of Interdisciplinary Bioscience and Bioengineering (I-Bio), Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea; Division of IT Convergence Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
Sanguk
S
Kim
Cancer Research Institute, Seoul National University School of Medicine, Seoul, Republic of Korea; Department of Biochemistry and Molecular Biology, Seoul National University School of Medicine, Seoul, Republic of Korea.
Junho
J
Chung
School of Interdisciplinary Bioscience and Bioengineering (I-Bio), Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea; Division of Integrative Bioscience and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
Sung Ho
SH
Ryu
D003198:Computer Simulation; D015195:Drug Design; D066246:ErbB Receptors / Q000737:chemistry*; D006801:Humans; D019151:Peptide Library; D011485:Protein Binding; D017434:Protein Structure, Tertiary
D019151:Peptide Library; C512478:EGFR protein, human; D066246:ErbB Receptors