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

ABSTRACT: 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 potent

SUBMITTER: Kim TY 

PROVIDER: S-EPMC7941009 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature