PROXIES

The use of PROXIES significantly enhances the robustness of (automated) NMR structure determination by allowing the NOE data corresponding to unassigned NMR resonances to be directly used in the calculations. The unassigned resonances are represented by additional atoms or groups of atoms that have no interaction with the regular protein atoms except through distance restraints. These so called 'proxy' residues can be used to generate NOE based distance restraints in a similar fashion as for the assigned part of the protein. If sufficient NOE information is available, the restraints are expected to place the proxies at a positions close to the correct atoms for the unassigned resonance, which can facilitate subsequent assignment. Convergence can be further improved by supplying additional information about the possible identities of the unassigned resonances. We have implemented this approach in the widely used automated assignment and structure calculation protocols ARIA and CANDID. We find that it significantly increases the robustness of structure calculations with regard to missing assignments and yields structures of higher quality. Our approach is still able to find correctly folded structures with up to 30% randomly missing resonance assignments, and even when only backbone and beta-resonances are present! This should be of significant value to NMR-based structural proteomics initiatives.

Details

Version:

1.0 (April, 2006)

Authors:

Eiso AB* and Alexandre Bonvin, Utrecht University

Contact:

Bijvoet Center for Biomolecular Research
Padualaan 8, 3584 CH Utrecht, the Netherlands
Email: a.m.j.j.bonvin@chem.uu.nl
Phone: +31-30-2533859
Fax: +31-30-2537623

*Current address:

Gorlaeus Laboratory, Leiden University
Einsteinweg 55, 2333 CC Leiden, the Netherlands
Email: e.ab@chem.leidenuniv.nl
Phone: +31-71-5274568
Fax: +31-71-5274593

We provide on this page the PROXIES libraries for use in CNS and CYANA, together with demo run data.

Reference:

F1000 evaluation
E. AB, D. J.R. Pugh, R. Boelens, R. Kaptein and A.M.J.J. Bonvin. " Direct Use of Unassigned Resonances in NMR Structure Calculations with Proxy Residues.",J. Am. Chem. Soc. (2006) 128(23) pp 7566 - 7571

Updates: 

We'll gradually add more scripts, library entries etc. to this site. If you want to be notified of updates send a mail to e.ab@chem.leidenuniv.nl with subject: proxy-update

Wikipedia: proxy

  • proxy:'... something which acts on behalf of something else ...'

In this case the proxy atoms (or residues) act on behalf of the atoms corresponding to the yet unassigned resonances. By assigning these unassigned resonances to proxies, they are supplied with coordinates, that can be subjected to geometric restraints, for example based on NMR data.

For questions, bugs, suggestions, contact: Eiso AB; e.ab@chem.leidenuniv.nl