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Residual_Grasp v1.0: Documentation
Preparation
These scripts restrict you to complexes consisting of exactly two
individual chains. These chains must be named A and B and
their coordinates and atomic information stored in a file called
complex.pdb in the working directory. The occupancy and B-factor fields
of complex.pdb will be ignored. If your ligand or receptor
consists of multiple segments or different chain identifiers, you can
manually rename chain identity in your complex.pdb file to obtain
the desired results. While tedious, this allows most of the rest of the
process to be automated.
It is necessary for two other files, complex.siz and
complex.crg also be in the working directory. These contain,
respectively, the radii and charges for the atoms in your complex.
Provided in this distribution are a set of example complex
files. complex.pdb contains barnase as molecule A and
barstar as molecule B. The complex.crg and
complex.siz are charge and radii files for this complex generated from
the CHARMM param19 parameter set [1].
Now, we set up GRASP for computation of the desired surface
potentials. Note, due to the finicky nature of GRASP's macro interpreter,
the computations to follow are broken down into several steps. You must
obtain your own copy of GRASP from the
Honig Lab at Columbia.
These macros were developed and tested with GRASP v1.3 running under SGI IRIX
5.3 and 6.2.
- Run GRASP.
- Right click on the main window and select "Read" from the menu.
Then select "Grasp Macro File" and type in the name of the macro file from
this distribution "residual.macros". The macros are now loaded. Note that
command sequences such as this shall be denoted Right click -> Read ->
Grasp Macro File -> residual.macros from now on.
- Right click -> Macros -> Residual Setup prepares GRASP by
eliminating the cross hairs, setting the inner dielectric constant to 4.0,
setting the bulk salt concentration to 0.145, and loading the pdb, crg and
siz files.
- You are now ready to start computing the surface potentials.
Treating Molecule A as the Ligand
Here we assume that molecule A is the ligand and molecule
B is the receptor. To obtain the Residual potential and its
components:
- Right click -> Macros -> Generate Surface of A creates the
molecular surface of molecule A and displays it. Tips:
- Right click -> Macros -> Background White creates a white or
gray background for your molecule.
- Right click -> Macros -> Background Black creates a black
background for your molecule.
- Right click -> Display -> Hide -> Bonds hides the stick
drawing of your complex, leaving only the molecular surface visible.
- Right click -> Macros -> Read Charges reloads all partial
atomic charges, preparing for the next step.
- Right click -> Macros -> Generate/Map/Store1 Unbound A
Potential computes the unbound potential of the ligand and displays it
on the surface (and saves it in General Property 1).
- Right click -> Macros -> Generate/Map/Store2 Bound A Potential
computes the bound potential of the ligand and displays it on the surface
(and saves it in General Property 2).
- Right click -> Macros -> Difference/Store1 Ligand Desolvation
Potential subtracts the unbound potential from the bound potential
yielding the desolvation potential. This potential is not displayed
(it is stored in General Property 1).
- Right click -> Macros -> Read Charges reloads all partial
atomic charges, preparing for the next step.
- Right click -> Macros -> Generate/Map/Store2 B Interaction
Potential computes the bound potential of the receptor on the ligand's
surface and displays it (and saves it in General Property 2).
- Right click -> Macros -> Compute Residual Potential
determines the sum of the interaction and desolvation potentials: this is
the Residual Potential. This potential is not displayed.
At this point, we have computed the Residual potential and its two
components, the ligand desolvation potential and the receptor interaction
potential. Their values are stored in GRASP's internal arrays
"potential," "property 1," and "property 2," respectively. You may now
use the three macros
- Right click -> Macros -> Display Desolvation Potential
- Right click -> Macros -> Display Interaction Potential
- Right click -> Macros -> Display Residual Potential
to view, manipulate and save each of these. The following steps are
usually taken:
- Each potential is mapped to a different scale (as shown on the
horizontal color bar on the screen). It is usually best to plot them on
the same scale, or at least ones which are comparable. For each
potential, Right click on the white window left of the horizontal
color bar -> Input Relative Values and enter the low, middle and high
potential values for the scale, something like "-60,0,30". Note, you
should be sure to use "0" for the middle value to separate colors
effectively. Note further that because the interaction and desolvation
potentials should be equal in magnitude and opposite in sign, if one scale
is (-60,0,30), then the other should be (-30,0,60).
- You may wish to use the mouse to rotate the surface so that the
active site is clearly visible.
- You may wish to use the macros described above to set the
background to white and hide the stick drawing of the receptor.
- Use the SGI snapshot utility to capture the image to an rgb
file.
Treating Molecule B as the Ligand
Here we assume that molecule B is the ligand and molecule
A is the receptor. To obtain the Residual potential and its
components are obtained analogously:
- Right click -> Macros -> Generate Surface of B
(Choose to replace the existing surface if it asks.)
- Right click -> Macros -> Read Charges
- Right click -> Macros -> Generate/Map/Store1 Unbound B
Potential
- Right click -> Macros -> Generate/Map/Store2 Bound B Potential
- Right click -> Macros -> Difference/Store1 Ligand Desolvation
Potential
- Right click -> Macros -> Read Charges
- Right click -> Macros -> Generate/Map/Store2 A Interaction
Potential
- Right click -> Macros -> Compute Residual Potential
At this point, we have computed the Residual potential and its two
components, the ligand desolvation potential and the receptor interaction
potential. Their values are stored in GRASP's internal arrays
"potential," "property 1," and "property 2," respectively. You may now
use the three macros
- Right click -> Macros -> Display Desolvation Potential
- Right click -> Macros -> Display Interaction Potential
- Right click -> Macros -> Display Residual Potential
to view, manipulate and save each of these. These images can be
manipulated in the same manner described above.
References
[1] CHARMM: A Program for Macromolecular Energy, Minimization, and Dynamics Calculations.
B. R. Brooks et al.
J. Comput. Chem.
4: 187-217 (1983).
Accessibility
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