515
15 (How to) Profit from Molecular Dynamics-based Ensemble Docking
In early applications, snapshots are extracted in a time interval of 10 ps for simulation lengths of 2 ns [80] or 22 ns [82], whereas in later applications every 20 ps for
simulations of lengths up to 50 ns yielding in hundreds to thousands of snapshots
for docking [43]. Consequently, docking runs for individual snapshots produce a
range of scoring values for each compound instead of single scores [41, 82, 84,
85]. Visualization of such scoring profiles over the simulation time shows the fluctuation of the docking scores and typically a histogram is generated for scoring
values (Fig. 15.4). We docked the approved drug zanamivir and an experimental
Fig. 15.4 Docking results: Typical score profile predicted by docking to 300 snapshots periodically extracted from several simulations of influenza neuraminidase over 30 ns sampling time for
a zanamivir and b compound 2, known to bind the open conformation of influenza neuraminidase.
The histogram visualizations (c, d) show that best scoring values are obtained with conformations
from the ligand-bound simulation. Docking poses ( black) discussed in the text are shown in comparison with native poses of zanamivir ( green) and compound 2 ( blue) (e–g)
15 (How to) Profit from Molecular Dynamics-based Ensemble Docking
In early applications, snapshots are extracted in a time interval of 10 ps for simulation lengths of 2 ns [80] or 22 ns [82], whereas in later applications every 20 ps for
simulations of lengths up to 50 ns yielding in hundreds to thousands of snapshots
for docking [43]. Consequently, docking runs for individual snapshots produce a
range of scoring values for each compound instead of single scores [41, 82, 84,
85]. Visualization of such scoring profiles over the simulation time shows the fluctuation of the docking scores and typically a histogram is generated for scoring
values (Fig. 15.4). We docked the approved drug zanamivir and an experimental
Fig. 15.4 Docking results: Typical score profile predicted by docking to 300 snapshots periodically extracted from several simulations of influenza neuraminidase over 30 ns sampling time for
a zanamivir and b compound 2, known to bind the open conformation of influenza neuraminidase.
The histogram visualizations (c, d) show that best scoring values are obtained with conformations
from the ligand-bound simulation. Docking poses ( black) discussed in the text are shown in comparison with native poses of zanamivir ( green) and compound 2 ( blue) (e–g)