title: Structure prediction of protein complexes by an NMR-based protein docking algorithm.
abstract: Protein docking algorithms can be used to study the driving forces and reaction mechanisms of docking processes. They are also able to speed up the lengthy process of experimental structure elucidation of protein complexes by proposing potential structures. In this paper, we are discussing a variant of the protein-protein docking problem, where the input consists of the tertiary structures of proteins A and B plus an unassigned one-dimensional 1H-NMR spectrum of the complex AB. We present a new scoring function for evaluating and ranking potential complex structures produced by a docking algorithm. The scoring function computes a 'theoretical' 1H-NMR spectrum for each tentative complex structure and subtracts the calculated spectrum from the experimental one. The absolute areas of the difference spectra are then used to rank the potential complex structures. In contrast to formerly published approaches (e.g. [Morelli et al. (2000) Biochemistry, 39, 2530-2537]) we do not use distance constraints (intermolecular NOE constraints). We have tested the approach with four protein complexes whose three-dimensional structures are stored in the PDB data bank (Bernstein et al., 1977) and whose 1H-NMR shift assignments are available from the BMRB database. The best result was obtained for an example, where all standard scoring functions failed completely. Here, our new scoring function achieved an almost perfect separation between good approximations of the true complex structure and false positives.
authors: Max-Planck-Institut für Informatik, Saarbrücken, Germany. oliver.kohlbacher@celera.com
authors: O
authors: O
authors: Kohlbache
authors: A
authors: A
authors: Burchardt
authors: A
authors: A
authors: Moll
authors: A
authors: A
authors: Hildebrandt
authors: P
authors: P
authors: Bayer
authors: H P
authors: HP
authors: Lenhof
mesh_terms: D000465:Algorithms; D000818:Animals; D002135:Calcium-Binding Proteins / Q000737:chemistry; D000252:Calcium-Transporting ATPases / Q000737:chemistry; D002147:Calmodulin / Q000737:chemistry; D003198:Computer Simulation; D005189:False Positive Reactions; D046911:Macromolecular Substances; D008958:Models, Molecular; D009414:Nerve Growth Factors / Q000737:chemistry; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D010446:Peptide Fragments / Q000737:chemistry; D011485:Protein Binding; D011494:Protein Kinases / Q000737:chemistry; D017434:Protein Structure, Tertiary; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D013816:Thermodynamics
chemical_list: D002135:Calcium-Binding Proteins; D002147:Calmodulin; D046911:Macromolecular Substances; D009414:Nerve Growth Factors; D010446:Peptide Fragments; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D011494:Protein Kinases; C106686:(CaM)-dependent protein kinase Ia kinase; D000252:Calcium-Transporting ATPases