A New Automated Method for Modeling Non-Covalent Macro-Molecular Interactions

Heteronuclear NMR and Soft Docking: An Experimental Approach for a Structural Model of the Cytochrome c553−Ferredoxin Complex

“…The ab initio procedure uses exclusively the interaction scoring function implemented in BiGGER (Figure 6A). As shown in a series of test cases (5), one should expect that this method will necessarily pinpoint the correct structure of the complex as one of the top ranking solutions of the docking. Then, the group of top-ranking solutions should rather be carefully analyzed.…”

“…Protein Docking. Molecular interaction simulations were performed using the docking program BiGGER (5). The docking procedure is composed of two modules that work in a sequence.…”

“…The second module (INTERACT) evaluates the population of putative solutions, according to four different interaction terms (surface matching, side chain contacts, electrostatic, and solvation energies) combined into a global scoring function and computed for every docked geometry. The program has been tested against a wide set of crystallographic protein-protein complexes (5) and it shows that a nearcorrect complex prediction is most often found within a reasonably small group of the top ranked solutions.…”

“…On the basis of 15 N and 1 H chemical shift variations, the mapping of an interaction site may be obtained. In the present work, we have developed a new approach where protein docking simulations, carried out with the program BiGGER (5), are associated to NMR mapping of the interaction sites to generate consistent models of electron-transfer complexes.…”

“…1 Abbreviations: NMR, nuclear magnetic resonance; NOE, nuclear Overhauser effect; NOESY, nuclear Overhauser effect spectroscopy; HSQC, heteronuclear single quantum coherence; BiGGER, bimolecular complex generation with global evaluation and ranking; BoGIE, boolean geometric interaction evaluation; PCR, polymerase chain reaction; DVH, DesulfoVibrio Vulgaris Hildenborough; FdI, ferredoxin I. to map the interacting site on the ferredoxin using induced chemical shift variations. A model of the ferredoxin was calculated and used for an ab initio docking simulation of the cytochrome c 553 -ferredoxin complex with the program BiGGER (5). NMR mapping of the interacting site on cytochrome c 553 and on ferredoxin was used as a filter to select the best structures resulting from the docking simulations.…”