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Filtering and selection of structural models: Combining docking and NMR
Author(s) -
Dobrodumov Anatoliy,
Gronenborn Angela M.
Publication year - 2003
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.10439
Subject(s) - docking (animal) , residual dipolar coupling , protein structure prediction , protein structure , computational biology , chemistry , computer science , biological system , nuclear magnetic resonance spectroscopy , biology , biochemistry , stereochemistry , medicine , nursing
It is generally accepted that protein structures are more conserved than protein sequences, and 3D structure determination by computer simulations have become an important necessity in the postgenomic area. Despite major successes no robust, fast, and automated ab initio prediction algorithms for deriving accurate folds of single polypeptide chains or structures of intermolecular complexes exist at present. Here we present a methodology that uses selection and filtering of structural models generated by docking of known substructures such as individual proteins or domains through easily obtainable experimental NMR constraints. In particular, residual dipolar couplings and chemical shift mapping are used. Heuristic inclusion of chemical or biochemical knowledge about point‐to‐point interactions is combined in our selection strategy with the NMR data and commonly used contact potentials. We demonstrate the approach for the determination of protein‐protein complexes using the EIN/HPr complex as an example and for establishing the domain‐domain orientation in a chimeric protein, the recently determined hybrid human‐ Escherichia. coli thioredoxin. Proteins 2003. © 2003 Wiley‐Liss, Inc.