[MMTK] Newby question

Michiel Jan Laurens de Hoon mdehoon at ims.u-tokyo.ac.jp
Thu Jul 10 18:25:34 EDT 2003

Dear everybody,

I have just started using MMTK, so forgive me if my questions are rather 
basic.  I am trying to estimate changes in the binding energy between 
the HIV protease and protease inhibitors due to mutations in the HIV 
genome.  The 1hsg PDB file contains the crystal structure of the 
protease complexed with the protease inhibitor Indinavir.  Using 
homology modeling, I can create PDB files with the estimated structure 
of a mutated HIV protease.  With MMTK, I try to estimate the binding 
energy as follows:

 >>> pdb = PDBMolecule('mutant.pdb')
 >>> inhibitor = pdb.createMolecule('BLK')
 >>> protease = Protein('mutant.pdb')

Now the PDB file does not contain the hydrogen atoms.  Is there a way to 
add those to the protease and the inhibitor from MMTK?

Then I try to calculate the energy:

 >>> universe = InfiniteUniverse(Amber94ForceField())
 >>> universe.addObject(protease)
 >>> protease_energy = universe.energy()
 >>> universe.addObject(inhibitor)
 >>> complex_energy = universe.energy()
 >>> universe.removeObject(protease)
 >>> inhibitor_energy = universe.energy()
 >>> binding_energy = complex_energy - inhibitor_energy - protease_energy

This fails because the Amber94 force field parameters are missing for 
the inhibitor.  Are such parameters available somewhere?  I didn't find 
them on the Amber web site, though I would think that Indinavir is a 
well-studied molecule.  Is it possible to mock up the interaction 
between the protease and the inhibitor?  Something quick and dirty is 
fine for what I am doing.

Many thanks in advance,

Michiel de Hoon,
Univsersity of Tokyo.

Michiel de Hoon, Assistant Professor
University of Tokyo, Institute of Medical Science
Human Genome Center
4-6-1 Shirokane-dai, Minato-ku
Tokyo 108-8639

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