Interleukin-2 superkines by computational design.

ABSTRACT: Affinity maturation of protein–protein interactions is an important approach in the development of therapeutic proteins such as cytokines. Typical experimental strategies involve targeting the cytokine-receptor interface with combinatorial libraries and then selecting for higher-affinity variants. Mutations to the binding scaffold are usually not considered main drivers for improved affinity. Here we demonstrate that computational design can provide affinity-enhanced variants of interleukin-2 (IL-2) “out of the box” without any requirement for interface engineering. Using a strategy of global IL-2 structural stabilization targeting metastable regions of the three-dimensional structure, rather than the receptor binding interfaces, we computationally designed thermostable IL-2 variants with

SUBMITTER: Ren J 

PROVIDER: S-EPMC8944926 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature