Desmond Tutorial

7 Preparing Free Energy
Perturbation
Overview
You can use Desmond to run free energy perturbation (FEP) calculations using the dual
topology approach to perform ligand mutation, annihilation, and single‐atom mutation in
a ring. From Maestro, you can visually specify the fixed and variable parts of a molecule
that are subjected to FEP calculations and then store the atom correspondence map
(which defines dual topologies) in the Maestro .mae file.
Ligand mutation—the most common FEP calculation—is illustrated in Figure 7.1 using a
typical scenario. The figure shows a graphical representation of the soluble form of the
human urokinase plasminogen activator receptor (sUPAR, PDB code 2fd6) and the ZINC‐
01538934 ligand. The protein structure has been processed using the Protein Preparation
Wizard and Prime as described in “Tutorial Steps” on page 3 and “Running Prime” on
page 29, respectively, and the ligand was docked using Schrödingerʹs Glide application as
part of a virtual screening experiment on the ZINC database (http://zinc.docking.org/).
The ligand is rendered in a tube representation in the sUPAR active site with green carbon
atoms and ball‐and‐stick representation.
September 2008 D. E. Shaw Research 69