Design of facilitated dissociation enables timing of cytokine signalling.

ABSTRACT: Protein design has focused on the design of ground states, ensuring that 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 because 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 focused on generating near-ideal structures^4-7. Here we describe a general approach for designing systems that use an induced-fit power stroke⁸ to generate a structurally frustrated⁹ and strained excited state, allosterically driving protein c

SUBMITTER: Broerman AJ 

PROVIDER: S-EPMC12611780 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature