FragMap Visualization

Visualizing SILCS FragMaps

Whether you used the SilcsBIO GUI or the 2c_fragmap command line utility to create SILCS FragMaps from your SILCS simulation trajectories, you will have a folder silcs_fragmap_<protein PDB>/maps that contains SILCS grid free energy (GFE) FragMaps for you system. SILCS FragMaps are defined using non-hydrogen atoms, and for certain solute types (imidazole, formamide) there are multiple FragMaps. FragMaps for water oxygen atoms (tipo) are created to identify water molecules that can be difficult to displace. Generic FragMaps for apolar (benzene+propane), H-bond donor (neutral H-bond donors), and H-bond acceptor (neutral H-bond acceptors) probe types are included to simplify visual analysis.

The easiest way to visualize FragMaps is with the SilcsBio GUI. SilcsBio also provides convenient FragMap visualization using MOE, PyMOL, and VMD.

FragMaps in the SilcsBio GUI

If you have used the SilcsBio GUI to run your SILCS simulations, once the simulations are complete, you will click the “Generate FragMap” button to automatically create FragMaps from the SILCS simulations, download them onto your local computer, and load them, along with the input PDB file, for visualization. Alternatively, you can load SILCS FragMaps from the Home page of the SilcsBio GUI:

If you are loading SILCS FragMaps from the Home page, you will be asked to select your FragMap directory (see File and Directory Selection). This directory has a standard name, silcs_fragmaps_<protein PDB>, where <protein PDB> is the name of the input PDB file. This directory was created on the server where you ran the SILCS jobs either when you clicked the “Generate FragMap” button or when you ran the ${SILCSBIODIR}/silcs/2c_fragmap prot=<protein PDB> command.

Alternatively, previously viewed visualization sessions may also be loaded by clicking on the checkmark next to the desired session under “Action”. The ten most recently viewed visualization sessions will be listed under “Recently viewed”. Frequently viewed sessions can be saved under the “Favorite list” by clicking on the star icon next to the session under “Action”. Additionally, extraneous sessions can be removed by clicking on the trash icon next to the session under “Action”.

Note

In addition to the FragMaps, the silcs_fragmaps_<protein PDB> directory contains the PDB file used to run the SILCS simulations. The SilcsBio GUI will automatically detect and load this PDB file. Additionally, if you have run Halogen SILCS, this directory will also contain the Halogen SILCS FragMaps, which will be automatically detected and loaded by the GUI.

Once loaded, the FragMaps and protein will be displayed with default settings. In the default settings, the protein is shown in cartoon representation and generic apolar, generic donor, and generic acceptor FragMaps are shown in green, blue, and red wire representation.

FragMaps can be toggled on and off by clicking the checkbox adjacent to the desired FragMap. Additionally, the FragMap GFE isosurface threshold can be increased or decreased using the + or - buttons. The default FragMap visibilities and FragMap GFE isosurface threshold cutoffs can be restored by clicking on the Reset to defaults button. The standard and halogen FragMaps and their associated probe atoms are listed in the tables below.

Table 1 Standard SILCS FragMaps

FragMap Name	FragMap Color	Component Name	Associated Probe Atom(s)
Generic Apolar	Green	apolar	Generic Apolar Carbons (benc+prpc)
Generic Donor	Blue	hbdon	Generic Hydrogen Bond Donors (forn+iminh)
Generic Acceptor	Red	hbacc	Generic Hydrogen Bond Acceptors (foro+dmeo+imin)
Positively Charged	Cyan	mamn	Methylamine Nitrogen
Negatively Charged	Orange	acec	Acetate Carboxylate Carbon
Hydroxyl Oxygen	Tan	meoo	Methanol Oxygen
Water Oxygen	Black	tipo	Water Oxygen
Benzene Carbon	Purple	benc	Benzene Carbons
Propane Carbon	Lime Green	prpc	Propane Carbon
Formamide Nitrogen	Blue	forn	Formamide Nitrogen
Formamide Oxygen	Red	foro	Formamide Oxygen
Dimethylether Oxygen	Red	dmeo	Dimethylether Oxygen
Imidizole Donor Nitrogen	Blue	iminh	Imidizole Nitrogen (h-bond donor)
Imidizole Acceptor Nitrogen	Red	imin	Imidizole Nitrogen (h-bond acceptor)

Table 2 Halogen SILCS FragMaps

FragMap Name	FragMap Color	Component Name	Associated Probe Atom(s)
Fluorbenzene	Blue	flbc	Fluorbenzene Fluorine
Chlorobenzene	Pink	clbx	Chlorobenzene Chlorine
Bromobenzene	Brown	brbx	Bromobenzene Bromine
Chloroethane	Green	clex	Chloroethane Chlorine
Fluoroethane	Green	fetx	Fluoroethane Fluorine
Trifluoroethane	Green	tfec	Trifluoroethane Carbon Bonded to Fluorines

The FragMap with the name “Exclusion Map” (component name “excl”) is a special case. The SILCS Exclusion Map enumerates all voxels where no probe molecule (including water) sampling occurred.

The representation of the protein can also be adjusted by clicking the “Protein” tab of the sidebar menu and toggling on or off the desired protein representations. The default protein representation can be restored by clicking on the Reset to defaults button.

When adding an additional representation, the default is to apply it to all atoms. It is possible to apply it to only a select set of atoms by clicking the “Components” tab of the sidebar menu, clicking the + adjacent to the protein structure name, and typing the atom selection in the blank box above the “cancel” and “confirm” buttons. The selection syntax is the same as for the NGL molecular structure viewer (see Atom Selection in the SilcsBio GUI).

It is also possible to load ligands for visualization. If the ligand file was the output of a SILCS-MC calculation, GFE values for the ligand atoms will be embedded within that file. These values can be visualized and their sum automatically computed by first loading the ligand file, and then using the “GFE” tab as detailed at the end of the section SILCS-MC Ligand Optimization Using the SilcsBio GUI.

FragMaps in MOE

To visualize your SILCS FragMaps with MOE, first create FragMaps in the MOE-readable CNS format. For this example, if your jobs ran on your server in the directory ~/silcsbio/projects/silcs.5tGP:

cd ~/silcsbio/projects/silcs.5tGP
$SILCSBIODIR/silcs/2c_fragmap prot=<protein PDB> cns=true

Note

This step is required ONLY for visualization with MOE. CNS format grid files are approximately 10x the size of the default-format grid files generated and used by your SilcsBio software. PyMol and VMD are capable of reading the default-format files, and, to save disk space, CNS format files are not generated unless specifically specified using the above command.

Running this command will create CNS format FragMap files in the silcs_fragmap_<protein PDB>/maps directory. It will also create the file silcs_fragmap_<protein PDB>/view_maps.svl. First, copy the entire silcs_fragmap_<protein PDB> directory from your server to a convenient location on the desktop or laptop machine where you will be doing the visualization. For example, on Linux or MacOS, you may use a command like

scp -rp silcsbio@silcsserver:~/silcsbio/projects/silcs.5tGP/silcs_fragmaps_3fly_fixed ~/Desktop

Then, use MOE to open the silcs_fragmap_<protein PDB>/view_maps.svl file by selecting File ‣ Open, which will bring up the “Open” window. In this window, browse to the silcs_fragmap_<protein PDB> directory, which, in this example, was downloaded from the server to the Desktop of the machine on which we are doing the visualization. Click the “CWD” button in the upper right corner to set this directory as the “Working Folder.” Then, select the view_maps.svl file and click the “Open” button:

MOE will process the view_maps.svl file to load your input PDB structure <protein PDB>.pdb used for the SILCS simulations, the CNS format FragMap files <protein PDB>.<fragmaptype>.map.cns, and the Exclusion Map <protein PDB>.excl.map.cns. The visualization of the FragMaps and Exclusion Map can be controlled in the “Surfaces and Maps” window, which is also automatically loaded by view_maps.svl.

FragMaps in PyMol

First, copy the entire silcs_fragmap_<protein PDB> directory from your server to a convenient location on the desktop or laptop machine where you will be doing the visualization. For example, on Linux or MacOS, you may use a command like

scp -rp silcsbio@silcsserver:~/silcsbio/projects/silcs.5tGP/silcs_fragmaps_3fly_fixed ~/Desktop

Open PyMol, then select File ‣ Open…, and open the view_maps.pml file located within the silcs_fragmaps_<protein PDB> folder. It is also possible to do this by typing commands into the PyMol console. For the silcs_fragmaps_3fly_fixed example here, the commands would be

cd /Users/silcsbio/Desktop/silcs_fragmaps_3fly_fixed

which sets the working directory, and

run view_maps.pml

which runs the view_maps.pml file in that directory.

Whichever of these two methods you use to load view_maps.pml, PyMol wil load the PDB structure <protein PDB>.pdb used for the SILCS simulations, the FragMap files, and the Exclusion Map. The visualization of the FragMaps and Exclusion Map can be controlled in the “PyMol FragMap Tools” window, which is also automatically loaded by view_maps.pml.

Warning

If your operating system associates the .pml extension with PyMol, it is possible simply to double click on the view_maps.pml file in the silcs_fragmaps_<protein PDB> folder. However, PyMol may fail to open multiple FragMaps. Specifically, if you are opening two different FragMaps having the same protein name, using double clicking to open view_maps.pml will result in the first FragMap being loaded again instead of the second one. Doing File ‣ Open… will direct you to provide the correct path for the second FragMap set.

FragMaps in VMD

First, copy the entire silcs_fragmap_<protein PDB> directory from your server to a convenient location on the desktop or laptop machine where you will be doing the visualization. For example, on Linux or MacOS, you may use a command like

scp -rp silcsbio@silcsserver:~/silcsbio/projects/silcs.5tGP/silcs_fragmaps_3fly_fixed ~/Desktop

Open VMD, select File ‣ Load Visualization State…, and open the view_maps.vmd file located in the silcs_fragmap_<protein PDB> directory you downloaded. A new window will pop up that says, “Select the folder where silcs_fragmap folder is downloaded”. Click the “OK” button and select the silcs_fragmap_<protein PDB> you downloaded.

Tip

Be careful to select the silcs_fragmap_<protein PDB> folder and NOT the silcs_fragmap_<protein PDB>/maps folder.

VMD wil load the PDB structure <protein PDB>.pdb used for the SILCS simulations, the FragMap files, and the Exclusion Map. The visualization of the FragMaps and Exclusion Map can be controlled in the “VMD FragMap Tools” window, which is also automatically loaded by view_maps.vmd.

Note

VMD (version 1.9.4 or older) does not read .map files correctly. It shifts the grid map by 1.73 angstrom. Visualization in PyMol is preferred.