Desmond Tutorial

Preparing Free Energy Perturbation
Adjusting the Conformation of the Mutant
NOTE
where:
• is the name of the job.
• is the maximum number of subjobs that can be submitted to a host or a
queue simultaneously. A value of zero means that there is no limit.
• is the number of CPUs per subjob, which can also be specified as, e.g., ʺ2 2 2ʺ
(note the quotes) indicating 8 CPUs with a spatial decomposition of 2x2x2.
• -HOST localhost means that the master job runs on your local workstation
whereas
• given with the -host option is the name of the host or queue where the
simulation jobs will be running.
To apply non‐default FEP λ parameters, add the ʹ-cfg config_fileʹ option to the
command syntax where config_file is a Desmond conguration file.
Note that this conguration file will be used throughout the .cmj workflow to make sure
that all minimization and MD runs use the same λ settings for consistency.
There is a Python script available, which can be used directly to compute the total free
energy difference associated with a FEP job. $SCHRODINGER/desmond-v.../bin/
Linux-x86/bennett.py will process the “energy” file output of the different λ runs
and compute the free energy. Use the --help option to learn about the use of this script.
Adjusting the Conformation of the Mutant
The initial conformation of the mutant must be as close as possible to that of the original
ligand for FEP simulations. Using Maestro, you can make manual adjustments to the conformation
or configuration of small molecules.
To show the mutant in its default conformation, click the button in the ʹViewʹ column of the
Fragment Library for the fragmentʹs row in the FEP Setup window. In Figure 7.8, the ʹViewʹ
option is selected for the butyl fragment.
Figure 7.8 Showing a mutant in its default conformation
Select the ‘View’ option to
show the mutant in its
default conformation.
September 2008 D. E. Shaw Research 77