Design of facilitated dissociation enables control over cytokine signaling duration.

ABSTRACT: Protein design has focused primarily on the design of ground states, ensuring they are sufficiently low energy to be highly populated¹. Designing the kinetics and dynamics of a system requires, in addition, the design of excited states that are traversed in transitions from one low-lying state to another^2,3. This is a challenging task as such states must be sufficiently strained to be poorly populated, but not so strained that they are not populated at all, and because protein design methods have generally focused on creating near-ideal structures^4-7. Here we describe a general approach for designing systems which use an induced-fit power stroke⁸ to generate a structurally frustrated⁹ and strained excited state, allosterically driving

SUBMITTER: Broerman AJ 

PROVIDER: S-EPMC11601400 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature