BV_MDSimulation

== Molecule Dynamic (MD) Simulation ==

In the following we show how to perform a molecule dynamic (MD) simulation for the N1 neuraminidase in complex with oseltamivir 2.

0.) Set the visualization model to the Ball and Stick model coloured by element. Display -> Display Properties

1.) Download the pdb structure 2HU4 via File->Open->Download PDB

2.) Delete all chains but chain A in the Structures window.

3.) Add hydrogens for the receptor by selecting the first chain A and Build->AddHydrogens

4.) Highlight the ligand by checking the second chain A and create a Ball+Stick by element- representation

5.) Focus on the newly created representation.

We want to manually assign the bond orders for the Oseltamivir ligand, therefore

6.) Switch to the Edit-Mode by Display->Edit Mode and change the accordant bond orders by right clicking on a bond and switching the bond order in the context menu.

Don't forget to switch back to the rotate mode Display->Rotate Mode

Now, we want to minimize the hydrogen atom positions in the ligand and receptor structure. First, we have to move the ligand to a seperate system.

7.) Therefore, first create a new System via Build->Create new molecule, then highlight the ligand (second Chain A), select Cut from the context menu, highlight the empty system and do Paste via the context menu.

8.) Now, select the the ligand system and do Build->Saturate with hydrogens

9.) Select all ligand H-atoms by element(H) in the expression bar

10.) Now, minimize the ligand's H-atoms by Molecular Mechanics->Energy minimization with MMFF94.

Next we want to minimize the receptor structure's H-atoms

11.) First change your view to the receptor representation, by doing Focus in the context menu of the accordant representation

12.) Next, select all H-atoms of the receptor by highlighting the receptor system and doing element(H) in the expression bar

13.) Then minimize the H-atoms Molecular Mechanics->Energy minimization using the AMBER force field.

Next, we want to do a MD-Simulation of Oseltamivir in the binding pocket. First, we want to highlight the binding pocket

14.) Therefore, we have to move the cut out ligand back into the receptor sytem, by highlighting the ligand structure, right click cut, highlight receptor system, right click paste

15.) Now, we identify atoms in the vicinity of the ligand. Select(!) the ligand structure and run the "selectNeighboringAtoms.py" script in BALLView's Python interpreter.

The script selects all atoms close to the ligand.

16.) Now, select these atoms by Highlight Selection in the contex menu of the Structures window.

Then, create a (SES/element)-Representation for the selection via the context menu.

Then, deselect the binding pocket atoms again.

17.) Now, regenerate a (BALL+Stick/element)-Representation for the ligand and a (Cartoon/SecondaryStructure) for the receptor.

18.) Select the ligand in the Structures window and highlight the receptor. Then initiate an MD-Simulation by Molecular Mechanics->Molecular Dynamic

Set stepsize to 0.0003, temperature to 400K and select the MMFF94 force field and start the simulation.

19.) Enjoy!