Desmond Tutorial

Preparing Free Energy Perturbation
Setting Up an FEP Calculation
Figure 7.4 Defining the mutation
The attachment bond is
shown as a green arrow in
the Workspace. The arrow
should point from the
core to the substitution
group.
NOTE
NOTE
3. Define the mutation to be performed by selecting the fragment(s) that will replace the
substitution group from the Fragment Library. For this example, select the butyl row
from the list of fragments. The selected row is highlighted in yellow as shown in
Figure 7.3.
You can apply multiple mutants at a time by using CTRL‐click and SHIFT‐click to
select the mutants from the Fragment Library. When you select multiple fragments, FEP
simulation creates different systems for each mutant, and runs multiple thermodynamic
cycles to compute, respectively, the binding free energy difference between the
reference ligand and each of the selected mutants, with respect to the receptor.
You can also create arbitrary groups rather than selecting mutations from the Fragment
Library. See “Creating a Custom Fragment Group” on page 80 for details.
4. Click the green Start button. FEP simulation starts execution.
Desmond uses Bennettʹs acceptance ratio method for FEP calculations, which means that
numerous independent simulations will be run for a single FEP calculation. Since the
independent simulations can be run simultaneously, you should be careful as to how
many simulations can be allowed to run on your host/queue at the same time. You can
control this parameter in the green Start window by setting the maximum number of subjobs
as shown in Figure 7.5. The value zero means no limit.
September 2008 D. E. Shaw Research 73