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 Discover notes.

The overall aim is to take an extended peptide and to introduce various different restraints before energy minimizing to force the peptide into certain desired conformations.

Step 1: Getting Started

1. Start up Insight, select the Discover module, and spend a few minutes browsing through the menus to familiarize yourself with the options.
   

Step 2: Building an Extended Peptide

1. Build a 14 residue peptide in an extended conformation. This tutorial will probably work better if you do not have any Gly or Pro residues in your structure.
   
   
2. Save this structure - your starting structure.
   

Step 3: Energy Minimization With No Restraints

1. Use Discover to energy minimize your starting structure.
   
   
2. Save your minmized structure under a new name.
   

Step 4: Minimization to an Alpha Helix Conformation

1. Go back to your starting structure.
   
   
2. Minimize into an alpha helical conformation in a series of steps by specifying H-bonding restraints appropriate for an alpha helix. It is realistic to restrain H-bonds in the range 1.8-2.0 Angstroms (the H to acceptor distance).
   In the first step, specify restraints corresponding to only the first turn of helix. Then minimize.
   In the next step, include restraints for the first two turns, then minimize, etc.
   
   
3. Save your final minimized structure.
   

Step 5: Minimization to a Beta-Hairpin Conformation

1. Go back to your starting structure.
   
   
2. Minimize the structure specifying a series of H-bonding restraints for H-bonds that you would expect to find in a beta-hairpin. Again it is best to do this in a series of steps, gradually building up the number of restraints. Try making the hairpin so that residues 7 and 8 are in the turn (i.e. they do not participate in H-bonds).
   
   
3. Save your final minimized structure under a new name.
   
   
4. If there is time, run another minimization specifying all the constraints for the beta hairpin at once. Compare the result to the result of doing stepwise minimization.
   

Step 6: Extensions

1. Minmization into 3-10 or pi helices
   
   
2. Minimization into a hairpin conformation starting from a helix
   
   
3. Comparison of different minimization algorithms.