We looked at sequences of virus proteins without a docking motif coincident with the spatial position of the standard motifs.
Dependence of the docking positioning accuracy is investigated as a function of parameters of the docking algorithm and the number of protein moveable atoms.
Compounds with the docking positions showing high-energy conformations, such as unreasonable angles and torsions caused by the steric effect, were excluded.
In order to gain insights into potential molecular determinants of compound specificity and starting points for compound variations in future development efforts, we analyzed the docking positions and orientations of 3 and 4 and differences in the respective binding sites between the Sirtuin isoforms.
These were ranked according to their docking scores, using methodology that was shown to achieve maximum accuracy (i.e., how well the docked position matched the experimentally determined site for ATP analogues in crystal structures of the complex).
Finally, all Ca2+-ions in the protein were redocked with AutoDock vina using default parameters, except for the "search space", ie, the volume in which the optimal docking position is searched for.
FOG1 was found to exhibit low stability after RbAp48 binding; the peptide displayed significant movement from the initial docking position, a phenomenon which matched the docking results.
Residue Arg-120 may be found in TM1 inside the cavity, close to the Pi docking position.
Those data could now be explained based on the findings of the docking predictions and biochemical analysis performed in the present study, indicating that Arg-201, which is close to the best docking position of glutamate, may at the same time be important for Pi transient binding and transport.
For the single-headed cross-bridges, we believe the companion head is either mobile or remains close to the relaxed state docking position on the thick filament shaft producing the residual density of the myosin shelves spaced 14.5 nm apart.
