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Untangling models reveals hidden information in structural data - James Holton

CCP4 171 2 weeks ago
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I present evidence that cooperative motions of functional dynamics can be extracted from ordinary, average electron density data using nothing more than established geometry restraint information. A robust scoring function is in hand, but an efficient approach to untangling the chains of multi- conformer models is needed. This underappreciated tangling phenomenon arises from the density term, not chemical geometry restraints, but nevertheless these tangles prevent current refinement programs from finding a way to simultaneously satisfy both kinds of data: observed density and prior knowledge of intramolecular forces. To demonstrate, I have prepared examples of a simple 2-state system with increasing degrees of tangling complexity. Moreover, the model with the best score reflects the true, underlying cooperative motion of the system, and the more untangled the model gets it both becomes closer it is to this true ensemble and it also becomes easier to detect the tangles. This finding implies that not only will untangling multi-conformer models lead to better geometry scores and lower R factors, but also reveal more biologically relevant cooperative motions. A global challenge data set with cash prizes will be announced.

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