Docking simulation, computational

If structural information of the protein target is available, e.g., a crystal structure, in silico screening of huge virtual compound libraries can be conducted by the use of docking simulations. Based on identified primary hits, structural variations of the ligand can be evaluated by computational modeling of the ligand-protein complex. 

M. Zacharias and H. Sklenar. Harmonic modes as variables to approximately account for receptor flexibility in ligand-receptor docking simulations Application to DNA minor groove ligand complex. Journal of Computational Chemistry, 20 287-300, 1999. 

J.-Y. TROSSETand H. A. Scheraga. Flexible docking simulations Scaled collective variable Monte Carlo minimization approach using bezier splines, and comparison with a standard monte carlo algorithm. Journal of Computational Chemistry, 20 244-252, 1999. 

Fig. 5 A cartoon illustration of ensemble docking, where five individual protein structures are superimposed to create a single scoring parameter for the docked ligand. Ensemble docking minimizes the computational effort since a single docking occurs to select the best conformer instead of five separate molecular docking simulations. (Reprinted with permission from [118], copyright 2007 by John Wiley and Sons)...

Shown below are snapshots of structures from our simulations of native RT with Sustiva and nevirapine. No crystal structure had been reported for RT with Sustiva when the calculations were performed however, confidence in the computed structure comes from the quantitative accord for the inhibition penalties and because Matador yielded docked structures for nevirapine, MKC-442, and 9-C1-TIBO that are virtually identical to the crystal structures.57 Sustiva hydrogen bonds with the backbone of K101, as do MKC-442 and 9-chloro-TIBO, and it has hydrophobic interactions in the Y181-Y188 pocket, also typical of NNRTIs. 

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