---
res:
  bibo_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 another2,3. 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 structures4,5,6,7.
    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 complex dissociation. X-ray crystallography, double
    electron–electron resonance spectroscopy and kinetic binding measurements show
    that incorporating excited states enables the design of effector-induced increases
    in dissociation rates as high as 5,700-fold. We highlight the power of this approach
    by designing rapid biosensors, kinetically controlled circuits and cytokine mimics
    that can be dissociated from their receptors within seconds, enabling dissection
    of the temporal dynamics of interleukin-2 signalling.@eng
  bibo_authorlist:
  - foaf_Person:
      foaf_givenName: Adam J.
      foaf_name: Broerman, Adam J.
      foaf_surname: Broerman
  - foaf_Person:
      foaf_givenName: Christoph
      foaf_name: Pollmann, Christoph
      foaf_surname: Pollmann
  - foaf_Person:
      foaf_givenName: Yang
      foaf_name: Zhao, Yang
      foaf_surname: Zhao
  - foaf_Person:
      foaf_givenName: Mauriz A.
      foaf_name: Lichtenstein, Mauriz A.
      foaf_surname: Lichtenstein
  - foaf_Person:
      foaf_givenName: Mark D.
      foaf_name: Jackson, Mark D.
      foaf_surname: Jackson
  - foaf_Person:
      foaf_givenName: Maxx H.
      foaf_name: Tessmer, Maxx H.
      foaf_surname: Tessmer
  - foaf_Person:
      foaf_givenName: Won Hee
      foaf_name: Ryu, Won Hee
      foaf_surname: Ryu
  - foaf_Person:
      foaf_givenName: Masato
      foaf_name: Ogishi, Masato
      foaf_surname: Ogishi
  - foaf_Person:
      foaf_givenName: Mohamad H.
      foaf_name: Abedi, Mohamad H.
      foaf_surname: Abedi
  - foaf_Person:
      foaf_givenName: Danny D.
      foaf_name: Sahtoe, Danny D.
      foaf_surname: Sahtoe
  - foaf_Person:
      foaf_givenName: Aza
      foaf_name: Allen, Aza
      foaf_surname: Allen
  - foaf_Person:
      foaf_givenName: Alex
      foaf_name: Kang, Alex
      foaf_surname: Kang
  - foaf_Person:
      foaf_givenName: Joshmyn
      foaf_name: De La Cruz, Joshmyn
      foaf_surname: De La Cruz
  - foaf_Person:
      foaf_givenName: Evans
      foaf_name: Brackenbrough, Evans
      foaf_surname: Brackenbrough
  - foaf_Person:
      foaf_givenName: Banumathi
      foaf_name: Sankaran, Banumathi
      foaf_surname: Sankaran
  - foaf_Person:
      foaf_givenName: Asim K.
      foaf_name: Bera, Asim K.
      foaf_surname: Bera
  - foaf_Person:
      foaf_givenName: Daniel M.
      foaf_name: Zuckerman, Daniel M.
      foaf_surname: Zuckerman
  - foaf_Person:
      foaf_givenName: Stefan
      foaf_name: Stoll, Stefan
      foaf_surname: Stoll
  - foaf_Person:
      foaf_givenName: K. Christopher
      foaf_name: Garcia, K. Christopher
      foaf_surname: Garcia
  - foaf_Person:
      foaf_givenName: Florian M
      foaf_name: Praetorius, Florian M
      foaf_surname: Praetorius
      foaf_workInfoHomepage: http://www.librecat.org/personId=dfec9381-4341-11ee-8fd8-faa02bba7d62
    orcid: 0000-0002-0806-8101
  - foaf_Person:
      foaf_givenName: Jacob
      foaf_name: Piehler, Jacob
      foaf_surname: Piehler
  - foaf_Person:
      foaf_givenName: David
      foaf_name: Baker, David
      foaf_surname: Baker
  bibo_doi: 10.1038/s41586-025-09549-z
  bibo_volume: 647
  dct_date: 2025^xs_gYear
  dct_identifier:
  - UT:001577755600001
  dct_isPartOf:
  - http://id.crossref.org/issn/0028-0836
  - http://id.crossref.org/issn/1476-4687
  dct_language: eng
  dct_publisher: Springer Nature@
  dct_title: Design of facilitated dissociation enables timing of cytokine signalling@
  fabio_hasPubmedId: '40993395'
...