C687 Tutorial: Molecular Dynamics & Simulated Annealing


The purpose of this tutorial is to learn how to do basic molecular dynamics using the Discover module.

The guidelines given in this tutorial are intentionally very loose. To prepare for this tutorial, read the InsightII Simulated Annealing notes. The overall aim is to do a simulated annealing run on the zinc finger structure.

This tutorial will be performed in the style of popular cooking shows: You set up the run (but don't actually run it), then you analyze the results of a run that I did earlier (there is not enough time to do the run and analyze it in one tutorial session).
All files relevant to the run can be downloaded:

This tutorial focuses on Lobodomide A, a potentially new type of antitumor lead optimization compound. Lobodomide A is shown below, and also shows the differences between Lobodomide A and Lobodomide B-F. In general, the Lobodomides consist of a macrocyclic ring and a long "main chain".

The General Structure of Lobodomides

Chad Bennett and I are currently modeling Lobodomide A. We ran a simulated annealing run to search for low-energy conformations, and we are currently analyzing the results to identify the pharmacophore. The pharmacophore is the region of the molecule that contains functional groups that are responsible for binding and binding specificity. We plan to compare the pharmacophore of Lobodomide A with the pharmacophore of Salicylihalamide A, a similar antitumor lead optimization compound.

The General Structure of Salicylihalamides

It is likely that the pharmacophores of Lobodomide A and Salicylihalamide A have the same functional groups. Can you identify these functional groups?


Part 1: Forcefields, Potentials, and Restraints

Duration: ~20 minutes
  1. Start InsightII and read in the bennett.pdb PDB file of lobodomide.
  2. Choose a Forcefield. See the Forcefield notes.
  3. Rename your molecule lobodomide.
  4. Fix/Fix/Fix all potentials and charges.
  5. Select the Discover module.

Part 2: Setting Up the Command File

Duration: ~20 minutes
  1. Select the Run/Run menu, and select the local workstation, input the molecule name, select COMMAND FILE, auto-assign parameters, only minimize, and Reduce Output. Then click EXECUTE. This step creates a .car, .inp, and .mdf file.
  2. Start a UNIX shell and read through the command file which has the suffix .inp. To understand each line in the file, follow through the bennett.inp example.
  3. At this stage, if you were actually going to perform a dyamics run you would edit the command file so that it would resemble the bennett.inp example file. However, for now it will suffice just to read through this example file and make sure you understand each command. Spend ~10 minutes doing this.
    Pay particular attention to the following features of the command file:


Part 3: Running the Dynamics

Duration: ~10 minutes

Read through the instructions about how you would submit this dynamics job and check on its progress.

This job was run on pchem03 with a "nice" number of 40. It took 20 hours, 24 minutes, 18.16 seconds of real time, starting at 9:25 am on a Wednesday. One other background job was also running on this workstation during this calculation.

Part 4: Analyzing the Results

Duration: ~40 minutes


Part 5: Verify that you have completed this portion of the assignment.

See the Energy Minimization & Molecular Dynamics Assignment page for details.
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Last updated: 01/23/2001