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Various strategies of using residual dipolar couplings in NMR‐driven protein docking: Application to Lys48‐linked di‐ubiquitin and validation against 15 N‐relaxation data
Author(s) -
van Dijk Aalt D.J.,
Fushman David,
Bonvin Alexandre M.J.J.
Publication year - 2005
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.20476
Subject(s) - chemistry , docking (animal) , residual dipolar coupling , residual , crystallography , molecule , intermolecular force , dipole , computational chemistry , nuclear magnetic resonance spectroscopy , stereochemistry , algorithm , computer science , organic chemistry , medicine , nursing
When classical, Nuclear Overhauser Effect (NOE)‐based approaches fail, it is possible, given high‐resolution structures of the free molecules, to model the structure of a complex in solution based solely on chemical shift perturbation (CSP) data in combination with orientational restraints from residual dipolar couplings (RDCs) when available. RDCs can be incorporated into the docking following various strategies: as direct restraints and/or as intermolecular intervector projection angle restraints (Meiler et al., J Biomol NMR 2000;16:245–252). The advantage of the latter for docking is that they directly define the relative orientation of the molecules. A combined protocol in which RDCs are first introduced as intervector projection angle restraints and at a later stage as direct restraints is shown here to give the best performance. This approach, implemented in our information‐driven docking approach HADDOCK (Dominguez et al., J Am Chem Soc 2003;125:1731–1737), is used to determine the solution structure of the Lys48‐linked di‐ubiquitin, for which chemical shift mapping, RDCs, and 15 N‐relaxation data have been previously obtained (Varadan et al., J Mol Biol 2002;324:637–647). The resulting structures, derived from CSP and RDC data, are cross‐validated using 15 N‐relaxation data. The solution structure differs from the crystal structure by a 20° rotation of the two ubiquitin units relative to each other. Proteins 2005. © 2005 Wiley‐Liss, Inc.