Desmond Tutorial

Desmond Tutorial
Tutorial Steps
Figure 1.10 Protein Preparation Wizard — Interactive H-bond optimizer
Click the ‘Analyze
Network’ button.
The OD2
oxygen atom is
protonated.
The table is filled
with the current
protonation
states of ASN,
GLN, and HIS
residues as well
as initial OH bond
orientations.
Click the ‘Lock’ option for a
residue to preserve its state.
The Workspace is
focused on the
selected residue.
Click the < and >
buttons to flip
through the
protonation states
and view changes
immediately in the
Workspace.
NOTE
NOTE
Select an item in the table to focus the Workspace on the selected residue. For example,
selecting item 8 in the table focuses the workspace on ASP50 as shown in
Figure 1.10. Originally, this ASP residue was charged. By pressing the < and > buttons
next to ASP50 in the table you can flip through all the different protonation states and
immediately view the result in the Workspace. Figure 1.10 shows the Workspace
when the OD2 oxygen atom is protonated (see the selected area). Similarly, residue
states and OH orientations of other residues can be set manually and, if desired,
locked by checking the Lock option.
Finally, by clicking the Optimize All button you can re‐optimize the hydrogen bonding
network. For further information about the Interactive H‐bond Optimizer click the
Help button.
14. Finally, provided that you have a Glide license from Schrödinger, the whole protein
structure in the Workspace can be subjected to constrained refinement by clicking the
Minimize button in the Impref minimization subpanel.
The preferred renement procedure for MD simulations is to use Desmondʹs own minimization/relaxation
protocol (see below).
The Protein Preparation Wizard cannot deal with the common case of missing side chains
and missing residues that often plagues PDB structures. Before using the Protein Preparation
Wizard, make sure that any missing parts of the protein structure are filled in. This
tutorial describes a method using Schrödingerʹs Prime application. See “Preparing Proteins
with Missing Residues or Side Chains” on page 29 for useful information on this
subject. You will need a license from Schrödinger to use Prime. In lieu of Prime, you
should use one of several tools available outside the Maestro environment.
15. The 4pti structure is now ready for preparing a Desmond simulation. Select
Applications > Desmond > System Builder as shown in Figure 1.11.
September 2008 D. E. Shaw Research 11