Desmond Tutorial

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Desmond Tutorial Desmond Tutorial Figure 1.9 Protein Preparation Wizard — Selection display The yellow dotted line shows the hydrogen bond. The selected water molecule is shown with a red oxygen atom. The selected item appears as a yellow line in the Workspace. 12. The Generate HET States button is used to automatically generate alternative protonation and tautomerization states for the HET groups. This is especially useful when ligands or cofactors are present in the system, but the current example does not have any such items. You will need a license from Schrödinger, LLC to use their Epik tool to perform automatic HET state generation. If you do not have an Epik license, you will have to prepare your ligands and cofactors outside the Maestro environment before you import the system into Maestro and process it with the Protein Preparation Wizard. 13. At this point you should have a topologically correct molecular system in the Workspace, which can be subjected to molecular mechanics calculations. However, since hydrogen atoms were added by the Protein Preparation Wizard using simple geometric templates, the hydrogen bond network should be optimized. There are two alternatives in the H-bond Assignment subpanel: — The Optimize button launches a comprehensive Monte Carlo search: different protonation states of ASN, GLN, and HIS residues are sampled and OH bonds are flipped to optimize hydrogen bond geometry. As part of this procedure you can switch to exhaustive search mode, as well as decide whether the orientation of crystal water molecules should be sampled. — The Interactive Optimizer button launches an interactive tool for hydrogen bond geometry optimization. The interactive optimizer window is shown in Figure 1.10. When you click the Analyze Network button, the Protein Preparation Wizard fills in the table with the current protonation states of ASN, GLN, and HIS residues as well as initial OH bond orientations. The table on Figure 1.10 reflects the current state after clicking the Optimize option. 10 D. E. Shaw Research September 2008
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
Page 1 and 2: Desmond Tutorial Desmond Version 2.
Page 3 and 4: Preface Intended Audience This tuto
Page 5 and 6: from outermost to innermost, separa
Page 7 and 8: Contents Preface . . . . . . . . .
Page 9 and 10: Loading Files from the Command Line
Page 11 and 12: List of Figures Figure 1.1: Simulat
Page 13 and 14: 1 Desmond Tutorial Introducing Desm
Page 15 and 16: Desmond Tutorial Tutorial Steps Fig
Page 17 and 18: Desmond Tutorial Tutorial Steps 3.
Page 21: Desmond Tutorial Tutorial Steps 11.
Page 25 and 26: Desmond Tutorial Tutorial Steps 18.
Page 27 and 28: Desmond Tutorial Tutorial Steps Sys
Page 31 and 32: 2 Learning the Maestro- Desmond Env
Page 33 and 34: Learning the Maestro-Desmond Enviro
Page 41 and 42: 3 Preparing Proteins with Missing R
Page 43 and 44: Preparing Proteins with Missing Res
Page 55 and 56: 4 Preparing a Desmond simulation wi
Page 57 and 58: Preparing a Desmond simulation with
Page 69 and 70: 5 Finishing Preparations for Desmon
Page 71 and 72: Finishing Preparations for Desmond
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Finishing Preparations for Desmond
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Finishing Preparations for Desmond
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6 Running Desmond Simulations Overv
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Running Desmond Simulations Running
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7 Preparing Free Energy Perturbatio
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Preparing Free Energy Perturbation
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8 Visualization and Analysis using
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Visualization and Analysis using Ma
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9 Analyzing Trajectories Using VMD
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Analyzing Trajectories Using VMD Lo
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Analyzing Trajectories Using VMD Ge
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Analyzing Trajectories Using VMD An
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10 Documentation Resources Detailed
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