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. You will need to figure out for yourself all the details of how you do these exercises. Refer to the InsightII Simulated Annealing notes.

The overall aim is to do a simulated annealing run on the zinc finger for which we built a homology based model in an earlier tutorial, and then to analyze the results of the run.

This tutorial will be performed in the style of popular cooking shows, i.e. 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 are in the directory /ruser/instruct1/stone/C687/MD and are labeled zf24.### (various files).

Step 1: Getting Started

1. Start up Insight and read in the file /ruser/instruct1/stone/C687/MD/zf1.psv This is the homology modeled zinc finger, energy minimized with the backbone fixed.
   

Step 2: Forcefields, Potentials, and Restraints

1. Choose a Forcefield
   
   
2. Check all potentials and charges
   
   
3. Open Discover
   
   
4. Fix the positions of the four zinc ligands (2 Cys and 2 His). Color fixed residues
   
   
5. Tether all backbone atoms with a force constant of 5.
   

Step 3: Setting Up the Command File

1. Click on Run/Run, and select the local machine, the molecule name, COMMAND FILE, auto-assign parameters, minimize, and Reduce Output. Then click EXECUTE .
   
   
2. Now go into a UNIX shell and read through the command file which has the suffix '.inp'. To understand each line in the file, follow through the example (zf24.inp).
   
   
3. At this stage, if you were actually going to perform a dyamics run you would edit the command file to make it look like the example file. However, for now it will suffice just to read through the 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:
   
   • Comment lines begin with an exclamation mark (!)
   • Parameters for changing the non-bond cutoff, the dielectric, and the decay time constant for heating and cooling.
   • Specification of tethered and fixed atoms
   • Initial quick minimization to reduce very high energies
   • Second, longer minimization before starting the dynamics
   • The equilibration step
   • The beginning and end of the dynamics loop
   • The steps within the dynamics loop
     
     • Heating and high temperature dynamics
       
     • Cooling and lower temperature dynamics (annealing)
       
     • First, quick minimization
       
     • Second, longer minimization
       
     • Recording the results
       
   
   
4. Also look at the files zf24.car and zf24.mdf which were created by Discover at the same time as the command file.
   

Step 4: Running the Dynamics

Step 5: Analyzing the Results