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Computational design of binding proteins to EGFR domain II.

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.

SUBMITTER: Choi YS

PROVIDER: S-EPMC3977815 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Computational design of binding proteins to EGFR domain II.

Choi Yoon Sup YS Yoon Soomin S Kim Kyung-Lock KL Yoo Jiho J Song Parkyong P Kim Minsoo M Shin Young-Eun YE Yang Won Jun WJ Noh Jung-eun JE Cho Hyun-Soo HS Kim Sanguk S Chung Junho J Ryu Sung Ho SH

PloS one 20140407 4

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 epid ...[more]

PMID: 24710267

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