Computationally-guided design and affinity improvement of a protein binder targeting a specific site on HER2

Cited 0 time in webofscience Cited 0 time in scopus
  • Hit : 32
  • Download : 2
A protein binder with a desired epitope and binding affinity is critical to the development of therapeutic agents. Here we present computationally-guided design and affinity improvement of a protein binder recognizing a specific site on domain IV of human epidermal growth factor receptor 2 (HER2). As a model, a protein scaffold composed of Leucine-rich repeat (LRR) modules was used. We designed protein binders which appear to bind a target site on domain IV using a computational method. Top 10 designs were expressed and tested with binding assays, and a lead with a low micro-molar binding affinity was selected. Binding affinity of the selected lead was further increased by two-orders of magnitude through mutual feedback between computational and experimental methods. The utility and potential of our approach was demonstrated by determining the binding interface of the developed protein binder through its crystal structure in complex with the HER2 domain IV. (C) 2021 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.
Publisher
ELSEVIER
Issue Date
2021
Language
English
Article Type
Article
Citation

COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL, v.19, pp.1325 - 1334

ISSN
2001-0370
DOI
10.1016/j.csbj.2021.02.013
URI
http://hdl.handle.net/10203/287534
Appears in Collection
BS-Journal Papers(저널논문)
Files in This Item
121442.pdf(0 B)Download

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0