Computer-guided binding mode identification and affinity improvement of an LRR protein binder without structure determination.

ABSTRACT: Precise binding mode identification and subsequent affinity improvement without structure determination remain a challenge in the development of therapeutic proteins. However, relevant experimental techniques are generally quite costly, and purely computational methods have been unreliable. Here, we show that integrated computational and experimental epitope localization followed by full-atom energy minimization can yield an accurate complex model structure which ultimately enables effective affinity improvement and redesign of binding specificity. As proof-of-concept, we used a leucine-rich repeat (LRR) protein binder, called a repebody (Rb), that specifically recognizes human IgG1 (hIgG1). We performed computationally-guided identification of the Rb:hIgG1 binding mode and leveraged the r

SUBMITTER: Choi Y 

PROVIDER: S-EPMC7485979 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature