Residual_Grasp v1.0: Documentation

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].

Here we assume that molecule A is the ligand and molecule B is the receptor. To obtain the Residual potential and its components:

1. 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.
2. Right click -> Macros -> Read Charges reloads all partial atomic charges, preparing for the next step.
3. 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).
4. 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).
5. 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).
6. Right click -> Macros -> Read Charges reloads all partial atomic charges, preparing for the next step.
7. 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).
8. 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.

• 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:

1. 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).
2. You may wish to use the mouse to rotate the surface so that the active site is clearly visible.
3. You may wish to use the macros described above to set the background to white and hide the stick drawing of the receptor.
4. Use the SGI snapshot utility to capture the image to an rgb file.

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:

1. Right click -> Macros -> Generate Surface of B (Choose to replace the existing surface if it asks.)
2. Right click -> Macros -> Read Charges
3. Right click -> Macros -> Generate/Map/Store1 Unbound B Potential
4. Right click -> Macros -> Generate/Map/Store2 Bound B Potential
5. Right click -> Macros -> Difference/Store1 Ligand Desolvation Potential
6. Right click -> Macros -> Read Charges
7. Right click -> Macros -> Generate/Map/Store2 A Interaction Potential
8. Right click -> Macros -> Compute Residual Potential

• 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.