Structure prediction of protein complexes by an NMR-based protein docking algorithm

Protein docking algorithms can be used to study the driving forces and reac tion mechanisms of docking processes. They are also able to speed up the le ngthy 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 te rtiary structures of proteins A and B plus an unassigned one-dimensional H- 1-NMR spectrum of the complex AB. We present a new scoring function for eva luating and ranking potential complex structures produced by a docking algo rithm. The scoring function computes a 'theoretical' H-1-NMR spectrum for e ach 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 pub lished approaches (e.g. [Morelli et al. (2000) Biochemistry, 39, 2530-2537] ) we do not use distance constraints (intermolecular NOE constraints). We h ave tested the approach with four protein complexes whose three-dimensional structures are stored in the PDB data bank [Bernstein et al. (1977)] and w hose H-1-NMR shift assignments are available from the BMRB database. The be st result was obtained for an example, where all standard scoring functions failed completely. Here, our new scoring function achieved an almost perfe ct separation between good approximations of the true complex structure and false positives.