button allows you to pause the simulation while looking at real-
time results in the PyMOL viewer. The “Stop” and “Abort”
buttons both end the simulation. However, stopping a simula-
tion generates final results while aborting does not. Stopping a
simulation can be particularly useful when the docking optimi-
zation has converged already to its minimum energy. FlexAID
also offers a way to continue a simulation from previously
generated results. When results are activated, the “Continue”
button may be clickable depending on the context (seeNote
32 ). It is possible to see these buttons at the top left corner of
theSimulatetab of the FlexAID interface.Click on the “Start” button to initiate the simulation. When
the genetic algorithm is under way, FlexAID updates the values of
fitness and scoring functions for the best individuals in terms of
scoring function. During the simulation, the PyMOL viewer is
updated with reserved objects (named TOP_<X>__, where X is
the Xth result predicted by FlexAID) displaying the actual best
results evaluated by FlexAID. These objects are temporary and
color-coded according to the “Color” column shown in the Flex-
AIDSimulatetab (seethe interface panel at the bottom right of
Fig.1). The NRGsuite offers a quick way of changing the display of
TOP_<X>__ complexes objects all at once instead of having to
manually update the display for the newly created objects. By
default, the target is displayed as “Cartoon” and the ligand as
“Sticks.” You can change these parameters as you like in the “Dis-
play options of TOP objects” in the top right corner of theSimu-
latetab of FlexAID. Whenever a reference is used (seestep 4above),
the “Last RMSD” column is updated at every refresh interval (see
step 6above about theGA Paramstab).
When a simulation is finished, or stopped, the reserved objects
RESULT_<X>__ and RESULT_<X>_H_BONDS__ are created
in the PyMOL viewer. RESULT_<X>__ are the complex’s objects
while the RESULT_<X>_H_BONDS__ objects are distances
objects displaying the h-bonds for the result. Their according
energy value (referenced as CF) and RMSD from the reference
(when one is used) of the results are displayed in the table shown
at the bottom right of Fig.1.
In the case where constraints are applied, an extra column,
Apparent CF, will appear which is a modified value of the CF to
reflect whether the predicted pose respects the desired constraints
imposed by the user.8.Analysis—Finally, look at the RESULT__X objects RMSD in
the last column of the FlexAIDSimulateresults table. Remem-
ber that this docking experiment serves as control with which
further docking experiments, e.g., different small molecules,
will be compared. FlexAID can retrieve RMSDs below 2.0 A ̊on378 Louis-Philippe Morency et al.