@article {109741,
	title = {Unsuspected pathway of the allosteric transition in hemoglobin},
	journal = {Proceedings of the National Academy of Sciences of the United States of America},
	volume = {108},
	year = {2011},
	pages = {5608-5613},
	abstract = {Large conformational transitions play an essential role in the function of many proteins, but expts. do not provide the at. details of the path followed in going from one end structure to the other.  For the Hb tetramer, the transition path between the unliganded (T) and tetraoxygenated (R) structures is not known, which limits our understanding of the cooperative mechanism in this classic allosteric system, where both tertiary and quaternary changes are involved.  The conjugate peak refinement algorithm is used to compute an unbiased min. energy path at at. detail between the two end states.  Although the results confirm some of the proposals of Perutz, the subunit motions do not follow the textbook description of a simple rotation of one αβ-​dimer relative to the other.  Instead, the path consists of two sequential quaternary rotations, each involving different subdomains and axes.  The quaternary transitions are preceded and followed by phases of tertiary structural changes.  The results explain the recent photodissocn. measurements, which suggest that the quaternary transition has a fast (2 μs) as well as a slow (20 μs) component and provide a testable model for single mol. FRET expts.},
	author = {Stefan Fischer and Kenneth W. Olsen and Kwangho Nam and Martin Karplus}
}
