QUANTA PRIMER 2

HANDLING MULTIPLE OBJECTS AND MOLECULES:

OPENING MULTIPLE FILES: It is often useful to examine two molecules at once
	 while using Quanta. This can be achieved by choosing OPEN from the
	 File menu, highlighting the desired files, and clicking on the OPEN
	 button. Alternatively, one can add a new file to a file already
	 displayed by opening the new file in the normal way and choosing the
	 ADD TO PREVIOUS SELECTION command from the dialog box that appears.

VIEWING MULTIPLE OBJECTS: When opened, the files displayed will be drawn
	 according to coordinates contained within each file. For this
	 exercise, the files used contain complementary coordinates. As a
	 result, opening the TRYPSIN file along with the BPTI file will
	 result in the correct geometry of the enzyme-substrate complex
	 being displayed, while simultaneous opening of homologous molecule 
	 files will result in the molecules being superimposed. Highlighting
	 the STAMP selection from the VIEW menu will separate the molecules by
	 placing them in different sections of the screen so that they can be
	 viewed individually. The molecules can also be manipulated separately
	 while in this mode by moving to the Molecular Management Window and 
	 clicking on the YES under the active column to change it to a 
	 NO to deactivate either molecule. Choosing the MONO command from the
	 VIEW menu will return the molecules to their complementary positions. 

DRAWING SURFACES: It is often useful to display the surface of molecules to
	 get a clearer view of the specificity pocket. Using a solvent surface
	 for the protein and a solid surface for the substrate seems to work
	 well.

	SOLVENT SURFACES:

	1)Calculating a New Solvent Surface: A solvent surface can be
		 generated by choosing SOLVENT SURFACES from under the
		 CALCULATE menu, then highlighting CALCULATE.
		 Select ALL ATOMS, then FINISH from the menu that will appear. 

	2) Displaying a Previously Generated Solvent Surface: A previously
		 generated surface for trypsin can be displayed by selecting
		 DISPLAY under SOLVENT SURFACES. Choose the file trypsin.srf
		 from the file list, then select ALL ATOMS, SINGLE COLOR, and 
		 LITTLE DOTS. (This surface is only valid for the trypsin.pdb
		 file and will not fit once this molecule has been mutated.)

SOLID SURFACES: A solid surface (also known as a CPK model) can be generated
	 by choosing the SOLID MODEL option from the DRAW menu. Select VAN DER
	 WAALS from the list of options. A solid model will be generated for
	 all molecules active at the time of the selection.

MUTATING RESIDUES:

Residue mutation can be accomplished through the PROTEIN DESIGN selection in
the APPLICATION MENU, which will open the PROTEIN DESIGN palette. From this 
palette, select EDIT PROTEIN. Highlight the MUTATE option, then select the
residue to be mutated by clicking on one of its atoms with the mouse. A dialog
box will appear listing the amino acid names. Choose the amino acid
that will replace the mutated one by highlighting it from the menu. The new
residue will replace the old. However, the new residue will not assume its
correct geometry.

MODELING SIDE CHAINS: 

ADJUSTING TORSIONS: Once a residue has been mutated, it is necessary to adjust
	 the torsions of its side chains to values which are likely to occur
	 naturally. This can be achieved using the MODEL SIDE CHAINS option 
	 from the PROTEIN DESIGN palette. Select the side chain to be modeled
	 by highlighting the CURRENT RESIDUE option in the MODEL SIDE CHAINS
	 palette and clicking on the desired side chain with the mouse.
	 Several options now exist:

	 MANUALLY ROTATE   allows user to adjust torsion angles manually using
			     the Dial Emulator
	 SPIN RESIDUE	   rotates through possible torsion angles in
			     30 degree increments until a conformation with
			     no close contacts is found
	 ROTAMER	   selects likely conformations based on parameters
			     specific to the rotamer chosen
	 NEXT CONFORMATION displays the next in a series of possible conformers

CHOOSING TORSIONS: Ideal geometry requires that the torsion angles, displayed
	 in the lower left side of the screen, be within thirty degrees of
	 either 60 or 180. Contacts (which can be displayed using the DISPLAY
	 CONTACTS option from the MODEL SIDE CHAINS palette) should be greater
	 the 1 Angstrom, and contacts should be small where atomic interaction
	 is desired. If the distance between two atoms of importance is not
	 displayed (which can be the case even when the atoms interact),
	 it can be calculated using the DISTANCE option from the GEOMETRY
	 palette.
 
SAVING COORDINATES: 

Two file options are useful for saving structures created with the PROTEIN
DESIGN palette. An MSF contains the names, types, charges, and three
dimensional coordinates of all of the atoms in the structure, as well as
information pertaining to residues and segments. A PDB file contains similar
information but is structured differently in order to be compatible with 
external databases such as the Brookhaven Protein Data Bank.

	MSF: An MSF containing the new residue and coordinate information
	 	can be created by choosing the SAVE TO MSF option from the
		EDIT PROTEIN palette or the SAVE AS option from the FILE menu.
		Choose a new name for the file.

	PDB: The information contained within an MSF file can be transferred
		into a PDB file by selecting the EXPORT option from the FILE
	 	menu, choosing the default options, and clicking on the EXPORT
	 	button.  Type any remarks to be saved with the file into the 
		dialog box that opens and then click on the OK button.