[Dock-fans] Amberscore after MD

Scott Brozell sbrozell at scripps.edu
Tue Aug 19 10:50:26 PDT 2008


On Sun, 17 Aug 2008, Francesco Pietra wrote:

> On Sun, Aug 17, 2008 at 12:27 AM, Scott Brozell <sbrozell at scripps.edu> wrote:
> >
> > On Fri, 15 Aug 2008, Francesco Pietra wrote:
> >
> >> For a protein and a ligand I carried out rigid docking, flex docking
> >> and amberscore with DOCK6. Then, the complex protein-ligand was
> >> embedded in a lipidic membrane for MD simulation with AMBER 10.
> >>
> >> At this point, I would like to carry out amberscore again. Is it wise
> >> to do that for the lowest_energy_structure captured from MD
> >> trajectories with ptraj? If so, working out manually the pdb file,
> >> extracting the parts related to the protein and the ligand for
> >> "Prepare" with Chimera.
> >>
> >> The alternative (which I tend to disfavor) is the averaged structure
> >> from the MD simulation.
> >>
> >> Or is anything better?
> >
> > The simple approach is to use the lowest_energy_structure, because the
> > averaged structure might not correspond to reality, and to eyeball
> > any structure as a basic check on reality.
> >
> > However, more complicated approaches may be better.
> > In general, one can usually find at least one metric for judging the
> > quality or appropriateness of the starting structure.
> > For example, sometimes a particular receptor functional group
> > interacts with a ligand.  One could form a histogram of the group-to-
> > ligand distance over the MD trajectory.  The shape of the histogram
> > would determine the set of starting structures: one big peak - pick
> > a structure from the peak bin; two separated but similar peaks -
> > now two starting structures would be necessary; etc.  Other metrics
> > might be ligand-centric or receptor-centric.
> That is interesting, albeit very laborious when the ligand is large
> and well docked, i.e., there are colse contacts (<= 3A) with many
> residues of the protein. If I understand, "one starting structure:
> means for both the ligand and the receptor. So, when many ...

It shouldn't be laborious to do some simple analyses since you already
have the trajectories.  For example, histograming a couple of ligand
dihedral angles and the closest receptor-atom-to-ligand-atom distance
from the lowest_energy_structure. 

> > Note that any MD geometry might not be very good, but that might not
> > matter.  Amber score is probably more sensitive to the geometry
> > than the other DOCK scores because MM interaction energies are
> > more forgiving of clashes, etc.
> > On the other hand, Amber score provides many levels of relaxation
> > of poor geometries, and using a real Amber MD snapshot would be
> > already relaxed.  So Amber scoring before and after DOCK docking
> > might be useful.
> I was looking at a setting for the time step. Is that to a default
> value? For a system where 0.0015 ps time step was used for MD in
> explicit solvent, what about for amber score?

The time step is 0.001: dt=0.001
Changing this would require rebuilding dock6 after editing score_amber.cpp


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