Editing Cooperative binding (section)

=== Conformational spread and binding cooperativity ===
Early on, it has been argued that some proteins, especially those consisting of many subunits, could be regulated by a generalized MWC mechanism, in which the transition between R and T state is not necessarily synchronized across the entire protein.<ref name=Changeux1967>{{cite journal | vauthors = Changeux JP, Thiéry J, Tung Y, Kittel C | title = On the cooperativity of biological membranes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 57 | issue = 2 | pages = 335–41 | date = February 1967 | pmid = 16591474 | pmc = 335510 | doi = 10.1073/pnas.57.2.335 | bibcode = 1967PNAS...57..335C | doi-access = free }}</ref> In 1969, Wyman<ref name=Wyman1969>{{cite journal | vauthors = Wyman J | title = Possible allosteric effects in extended biological systems | journal = Journal of Molecular Biology | volume = 39 | issue = 3 | pages = 523–38 | date = February 1969 | pmid = 5357210 | doi = 10.1016/0022-2836(69)90142-9 }}</ref> proposed such a model with "mixed conformations" (i.e. some protomers in the R state, some in the T state) for respiratory proteins in invertebrates.

Following a similar idea, the conformational spread model by Duke and colleagues<ref name=Duke2001>{{cite journal | vauthors = Duke TA, Le Novère N, Bray D | s2cid = 14914075 | title = Conformational spread in a ring of proteins: a stochastic approach to allostery | journal = Journal of Molecular Biology | volume = 308 | issue = 3 | pages = 541–53 | date = May 2001 | pmid = 11327786 | doi = 10.1006/jmbi.2001.4610 }}</ref> subsumes both the KNF and the MWC model as special cases. In this model, a subunit does not automatically change conformation upon ligand binding (as in the KNF model), nor do all subunits in a complex change conformations together (as in the MWC model). Conformational changes are stochastic with the likelihood of a subunit switching states depending on whether or not it is ligand bound and on the conformational state of neighbouring subunits. Thus, conformational states can "spread" around the entire complex.