The Biopolymer module provides for specialized treatment of macromolecular structures and systems. ComposerTM, MatchMaker and GeneFold all provide different approaches to the problems of Protein Folding, Sequence, and Structural Similarities. ProTable enhances the SYBYL "Molecular Spreadsheet" for the analysis of protein structural integrity. The GASP, RECEPTOR, and DISCO modules provide techniques for conformational searching and for pharmacophore recognition and analysis. Quantitative Structure Activity Analyses is supported by the QSAR, Advanced CoMFA, and HQSAR modules. FlexX and FlexiDock allow investigation of the configurations necessary for ligand binding to protein receptors. These modules and several more are described in more detail at the Tripos website.
Starting SYBYL on the CBCL Cluster
To start SYBYL, open a UNIX shell window and type sybyl at the command line. To read a file in PDB format, click on Biopolymer in the main SYBYL menu bar, then Brookhaven, then Read. You may have to define or specify the path to the PDB file you wish to read.
PDB files may be read in, manipulated and visualized by SYBYL, although files of coordinates in several other formats may also be read. SYBYL runs only on UNIX-based machines.
It will probably be convenient to have Netscape running in another window since documentation for the various Tripos modules can be accessed though the web browser.
The SYBYL Display
Mouse Operations
Reading a Structure File
Selecting Atoms, Residues
and Molecules
Controlling the Display
Changing How the Atoms are Displayed
Calculate and Display
the Hydrogen Bonds
Clear Display of H-bonds
Examine Folding Using a Ribbon
Figure
Clear Display of the Ribbon
Display a van der Waals
Molecular Surface
Analyzing a Structure
List Bond Distances or Angles
EXIT SYBYL
Help, Tutorials
Return
to the Main Page
The SYBYL Display. There are several things to notice about the SYBYL screen when it first comes up. The first is the list of menu names horizontally arrayed across the top. Second is the column of icons at the left edge. The third icon provides a means of quickly changing the display mode (ball-and-stick, space-filling, and so forth). The fifth icon allows adjustment of details of how molecules are rendered, including selection of colors for the molecular components and the background. The icon with a cross in it permits rotations and translations about each Cartesian axis. All of these left-column icons remain displayed once they are clicked on until the Q (for quit) button in the icon window is clicked. You can explore the functioning of the remaining buttons is this column at your leisure.
The Unix shell window that you started SYBYL from remains open and becomes the text window for the program. Output from the various program functions will appear here and commands for SYBYL can be entered here when the SYBYL prompt (Sybyl>) is present.
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Mouse Operations. The z-axis of a drawing in perpendicular to the screen and the x and y axes lies in the plane of the screen. You can also zoom and rotate by using combinations of mouse buttons. By default:
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Reading a Structure
File
Click on Biopolymer to bring up
the choices on this menu.
Click on Brookhaven File, then
READ.
SYBYL lets you have a number of molecular structures present simultaneously. These are held in "molecular areas" labeled M1, M2, ?. Select M1 to hold the first molecule by clicking on this. The Brookhaven file menu comes up.
Specify the directory path to the PDB file desired PDB file name. Click on the file name. For this example, it will be assumed that the file double_helical_dna.pdb was selected.
SYBYL will ask about centering the molecule. This is generally desirable since rotations take place about the geometrical center of the structure and are therefore more likely to remain in view on the screen.
Zoom and rotate so that the molecule is displayed in the drawing window. The drawing may appear faint or may partially disappear in this process. This is because the z-clipping is set inappropriately. To adjust z-clipping, click on the eighth icon from the top on the vertical array of icons on the left side. Choose ZClip Everything and change the width and mid-point of the z-slab by clicking on the increase or decrease arrows until the display is satisfactory.
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Selecting
Atoms, Residues and Molecules
Several functions controlling the nature of the molecular display require
selection of all or part of a structure. In these instances, three menu
buttons will come up (as part of a larger menu): Sets,
Atom
Types and Substructures.
SETS
are reasonable groupings of substructures such as sidechains or backbone.
Some are built-in, others are defined because of the nature of the molecule,
and still others can be defined by the user. One or more sets can be selected
by clicking on the small box next to their name or by clicking on their
name in the list provided. The Atom Types
menu can be used for selection of certain atoms in a structure, for example
all aromatic carbon atoms. Substructures
are
the amino acid or other subunits that make up the biopolymer. These are
listed in the order in which they appear in the primary sequence. A particular
subunit is selected by clicking on its name, followed by OK. Finally, simply
positioning the cursor on or very near the atom on the screen and clicking
can make selection of individual atoms.
After a selection by any of these methods has been made, small squares or diamonds on the displayed molecule will mark the atoms selected. (The Highlight option has to be switched on; being on is the default setting.) If a mistake has been made, a selection can be undone by clicking on Undo and then OK. There is also a facility for clearing all selections.
Boolean combinations for selections are possible--click the button labeled Union to implement one of these. The Invert button selects all of those atoms not selected by previous selection methods; clicking Invert twice gets you back to the original selection.
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Controlling the
Display
Coloring by atom type
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Changing
How the Atoms are Displayed
The simplest way to change the way a structure is displayed is to click
on the third menu item from the top in the left-hand vertical column. You
can select the rendering method (Space Fill, Ball & Stick, Stick or
Lines) there. Examine each of these renderings of the DNA structure. Note
that attempting to rotate or translate any rendering other than Lines
has a slow response, very slow in the case of the Space Fill rendering.
For a more selective application of a rendering method click on View >>> Mixed Rendering? Select the kind of representation to be used from the list that comes up. Chose one of these and click OK. Now a selection menu comes up. Choose the Pyrimidine set and click OK. (You should see the pyrimidines of the DNA structure marked with diamonds. Click OK and the pyrimidines will be rendered with the selected method. Select the atoms to be changed.
To get back to a simple wire frame display of the DNA molecule, click View >>> Delete All Backgrounds.
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Calculate
and Display the Hydrogen Bonds
Add hydrogens to the structure: click Biopolymer
>>> Add Hydrogen? >>> All
>>> OK. Select to add ALL
hydrogens when asked.
Click View >>> Display H-Bond >>> Static.
Another selection menu comes up. Choose All and then OK. Finally, another menu comes up for selection of the color of the dotted line that will represent the hydrogen bond. Choose your favorite and click OK. Hydrogen bonds between the base pairs of the DNA should now be rendered by dashed yellow lines.
Note that one could have different types or classes of hydrogen bonds colored in different ways by repeating this sequence and making different selections.
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Clear Display of
H-bonds
To erase the hydrogen bonds and get back to a simple wire frame display
of the DNA molecule, click View >>>
Delete
All Backgrounds.
Now delete the DNA molecule by the sequence Build/Edit >>> Zap (Delete) Molecule.
Click Biopolymer >>> Build >>> Protein. Then click on Cancel. Read in the PDB file for the BPTI protease structure (bpti.pdb). Color the drawing according to atom type.
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Examine
Folding Using a Ribbon Figure
Select Biopolymer >>> Display >>> Shaded
Ribbon.
Another selection menu comes up. The various ribbon displays possible are listed; select Shaded Ribbon...
Click on Chain A then drag with the left mouse button depressed until the entire chain A sequence has been highlighted. Click OK. (The ribbon will eventually be drawn through only the A-chain of the structure.)
Now a menu for selection of the ribbon color appears. Choose a color and the click OK.
The process can be repeated in order to create and color a ribbon or other rendering of Chain B of the HIV protease structure.
To remove the display of the individual atoms, View >>> Undisplay Atoms ?. >>>. Then select All and OK from the selection menu that comes up. One could at this point choose to undisplay only a part of the structure.
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Clear Display
of the Ribbon
To erase both ribbons and get back to a simple wire frame display of
the HIV protease dimer, click View
>>>
Delete All Backgrounds. If you
want to remove only one of the ribbons, click View
>>> Backgrounds >>> Delete. A listing of the various ribbons (renderings)
that have been made appears and a choice can be made regarding which one(s)
to remove.
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Display
a van der Waals Molecular Surface
Select View >>> Dot Surfaces? >>> vdw
Dot Surface?. Select the atoms which will be surrounded by the dots
representing the van der Waals surface and then select the color to be
used for the dots. Return to the top of this
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Notes: (1) In SYBYL the dots for a dot surface are stored in a file and retained as a "background" which can be turned on and off or re-colored in the same way that ribbon or other representations are retained and manipulated. There can be several dot surface files for the same or different parts of the molecule and these can be colored as one wishes.
(2) The density of dots per square Angstrom is set at 12. This density can be changed through the use of the "tailor" function in SYBYL. Click Options >>> Tailor >>> Set >>> DOTS >>> DENSITY to get a menu that will let you change this parameter.
(3) Construction of the Connolly solvent accessible surface although listed in the SYBYL menu does not execute since a required piece of software has not been installed. It should be possible to change the parameters used in the van der Waals surface calculation to get a result similar to the Connolly surface but this has not been explored.
(4) There is considerable computation involved in producing "dot surfaces". Be prepared for a delay when creating a dot surface for a large molecule.
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Analyzing a Structure
Measure selected bond lengths and angles
Select the Analyze menu, then Measure.
Note the different possibilities for "measurement". Select Distance.
This function will report the distance between two atoms. The atoms may be selected by typing their names at the appropriate line in the menu that comes up or, more conveniently, just by pointing and clicking the left mouse button. After selection the distance between the atoms selected appears in the window where SYBYL was started.
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List Bond
Distances or Angles
Select Analyze >>> Measure
>>> Topography.
Select the class of parameter to be listed from the menu that appears and click OK. Now a selection menu comes up and one can select for which part of the structure the selected parameter will be listed. After clicking on OK a listing of the requested information appears in the window where SYBYL was started.
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EXIT SYBYL
To leave the program, make sure to save any data that you wish to retain.
Then click File >>> Exit
SYBYL.
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Help, Tutorials
There is extensive documentation available from Tripos for SYBYL and
its associated modules. To view this on the CCBL system, open Netscape
and then open the (local) file /usr/local/spec/sybyl/ TriposBookshelf/sybyl/index.html.
to
view the index to the Tripos written documentation. (You will probably
want to add this URL to your Bookmarks in Netscape.) Alternatively, click
on the Help button at the upper right
of the screen and choose Start Browser.
When Netscape is running, return to the Help
menu and select Start Bookshelf.
There are tutorials for many modules available. Tutorials and documentation may be accessed through the web browser or obtained as printable (PDF) files. Under SYBYL Introduction, choose and work through the Conventions & Terminology tutorials. Then switch to Biopolymer under the Biopolymer Modeling listing and work through the Displays tutorial.