This chapter describes building and modeling applications accessed through the Applications menu. These applications extend the capabilities of QUANTA for particular types or forms of molecules or for particular approaches to modeling. The applications include:
All these applications are supplied as optional packages with core QUANTA.
Read this chapter or portions of it to become familiar with how to access and use any of these applications. Additional documentation is available for optional applications. See the preface for a complete list of QUANTA and QUANTA-related documentation.
Crystal Modeling provides tools to generate and modify a system based on translational periodicity or crystallographic symmetry. Crystal Modeling can interactively build periodic or crystalline structures from:
Crystallographic spacegroups can be used to create symmetry-related copies of the original molecule. The appropriate symmetry information can be sent to CHARMm.
Crystal Modeling operates in two modes: real atom mode and symmetry atom mode. In real atom mode, symmetry copies extend the size of the structure by creating new atoms. The size of a system generated in real atom mode is subject to the normal QUANTA atom limits.
In symmetry atom mode, symmetry copies exist only as abstract data. No physical atoms are created. Any changes to the asymmetric unit are immediately reflected in the symmetry copies. Symmetry atoms are displayed as graphical objects and cannot be picked or manipulated as real atoms can.
Symmetry information can be saved to an atom selection file, filename.asd, and used subsequently in Crystal Modeling to generate symmetry copies. Symmetry information can also be sent to CHARMm to obtain a correct energy computation for the crystal. Once CHARMm is provided with symmetry information, subsequent energy minimization and dynamics operations also use symmetry images in their calculations. Crystal Modeling additionally provides a tool to perform lattice optimization in CHARMm, where CHARMm minimization modifies the unit cell parameters as well as the atom positions to optimize the crystal structure.
The atoms selected in QUANTA just before entering Crystal Modeling are used as the template from which symmetry-related copies are built. Although a structure might have its own internal symmetry, this atomic system is referred to as the asymmetric unit. If CHARMm calculations are to be performed on the crystal, the asymmetric unit must be an MSF.
When you exit Crystal Modeling, symmetry copies can be retained or discarded. When they are retained, additional modeling, including minimization, dynamics, and conformational searches, can be carried out on the molecular structure in the crystalline environment. However, all symmetry copies should be removed before attempting to reenter Crystal Modeling to correctly calculate CHARMm images.
As you enter the Crystal Modeling application, it detects whether the MSF contains symmetry information. If there is no symmetry information in the current MSF, a dialog box displays a list of spacegroups available in the symmetry library file $HYD_LIB/symlib.sym.
This file lists symmetry operators that generate all equivalent positions in a unit cell for each of the standard spacegroups. The list of available space groups can be expanded to include nonstandard settings by editing the symmetry library file and adding the appropriate information.
When the MSF contains symmetry information, an opportunity to use this information or select another space group is offered. If symmetry information stored in the current MSF is not used, a new MSF is created to store the specified symmetry information with the molecular structure. A dialog box is displayed offering MSF saving options.
The initial unit cell dimensions (a, b, c, a, b, g) must be specified. Enter only the dimensions that can be defined independently for a given spacegroup. If spacegroup C2 is selected, for example, a dialog box is displayed to enter the unit cell dimensions a, b, c, and b.
In some cases, you are also prompted to define a unique axis by providing an orthogonalization method code. Orthogonalization codes determine the orientation of the unit cell axis and its reciprocal (abc and a*b*c*, respectively), with respect to the xyz modeling axis. The orthogonalization code is usually set to 1. Table 26 lists the codes and their definitions.
Crystal Modeling allows the asymmetric unit to be modified while symmetry copies exist. Symmetry copies are updated to reflect modifications in the asymmetric unit. When Modify Asymmetric Unit is selected, a palette is presented to provide a specific set of selections for this function.
The Crystal Modeling palette provides selections for interactively generating a crystal by creating symmetry copies, displaying the unit cell, and changing the unit cell dimensions. The palette also provides access to CHARMm for calculating the energy of the crystal structure and creating symmetry images. Table 27 lists the palette selections and provides a brief description of each.
CHARMm makes symmetry copies of a primary molecule or collection of molecules by creating a set of images. Each image is given a unique name and a set of instructions. These instructions are in the form of matrices describing the rotation and translation needed to generate the image.
The CHARMm Energy/Image selection creates a CHARMm image file and sends it to CHARMm with a request for the energy of the crystal structure. This file includes the coordinates of the asymmetric unit and the image commands needed to generate a crystal identical to the one displayed in the viewing area.
Update Parameters in the CHARMm menu is used in this calculation and should be set prior to starting Crystal Modeling. Appropriate values for Image Update Frequency and Image Cutoff Distance are specified in the Update Parameters dialog box.
The energy computed when images are in effect includes the intra-molecular energy of the asymmetric unit alone, plus the interaction energy between the asymmetric unit and image atoms falling within the image cutoff, each interaction being evaluated only once.
If the cell constants or other parameters defining the crystal are subsequently changed, the CHARMm image file is also updated. The modified image file is used in subsequent selections of CHARMm Energy/Image.
After the selection is used, you can exit Crystal Modeling and perform more extensive CHARMm calculations on the displayed crystal in the Molecular Modeling application. All modeling operations including minimization, dynamics, and conformational search can be performed with the CHARMm images in effect, preserving the specified crystal symmetry.
During energy minimization or molecular dynamics, the atoms of the asymmetric unit and the symmetry copies are displayed in the viewing area. However, only coordinates for the atoms of the asymmetric unit are written to the dynamics trajectory files. Despite the fact that all atoms are not explicitly present, the energies reported are those of the molecular structure in the defined crystalline environment.
CHARMm energies for a collection of real atoms differ from those obtained using image data. The energy reported when all atoms are physically present includes an intra-molecular energy term for each of the symmetry copies and all pairwise interactions between copies falling within the prescribed nonbond cutoff.
When image data is in effect, only the intramolecular energy term for the asymmetric unit is calculated, in addition to all interactions between the asymmetric unit and image atoms falling within the cutoff range.
Nevertheless, reliable conformational modifications, such as minimizations, can be performed using energies obtained with CHARMm images.
In subsequent QUANTA sessions, the image file created in Crystal Modeling can be sent to CHARMm. This is accomplished by renaming the image file (charmm.img) to charmm_img.str, so that it is recognized as a stream file. The Stream CHARMm File selection in the CHARMm menu can then send the file to CHARMm. These image files function correctly only when the original asymmetric unit is displayed in the viewing area.
The Modify Asymmetric Unit selection provides a way to modify the asymmetric unit in Crystal Modeling while retaining the crystal symmetry. When you make this selection, the Modify Asymmetric Unit palette opens over the Crystal Modeling palette. Selections on this palette are listed in Table 28. A torsion template file must be selected prior to modeling the asymmetric unit. When you select Read Torsion Template from the Model Asymmetric Unit palette, a File Librarian allows you to select the file that defines adjustable torsions. Torsions that are part of a ring system or cyclic structure should not be defined in a torsion template file.
The Model Asymmetric Unit palette contains selections for rotating and translating the entire molecular structure or changing specific torsions. If you select Rotate Atoms or Translate Atoms, a palette opens over the Model Asymmetric Unit palette. These palettes contain adjustable torsions displayed as selections.
The Rotate and Translate selections cause a transformation of the asymmetric unit to occur. The unit of change is degrees when Rotate is active and angstroms when Translate is selected.
In the following exercise, Crystal Modeling procedures define a spacegroup, specify unit cell dimensions and orthogonalization code, specify lattice translations, display symmetry copies, and incorporate symmetry information into an MSF. For this exercise, build the structure nitrobenzene in ChemNote. If you have not completed Chapter 1 on 2D structure sketching, do so before you continue with this exercise.
1. Create a structure to use in generating a crystal.
Display the Applications menu and select Builders. From the pull- right menu, select 2D Sketcher. The ChemNote window is displayed.
Sketch the structure nitrobenzene.
2. Return to Molecule Modeling mode with the structure.
Display the ChemNote File menu and select Return to Molecule Modeling. A dialog box asks if the changes should be saved.
Select Yes and the File Librarian dialog box is displayed.
Enter the text nitrobenzene and click Save. A dialog box is displayed offers several options for adjusting partial charges.
The desired net charge is: 0.000
CT, CH1E, CH2E, CH3E, C5R, C6R, C5RE, C6RE, HA types
The ChemNote window is removed from the screen, revealing the Molecular Modeling window. When the conversion of nitrobenzene.mol to nitrobenzene.msf is complete, a dialog box offers options for displaying MSFs.
Use the new molecule nitrobenzene.msf only
Click the OK button, and the nitrobenzene structure is displayed in the viewing area.
3. Setup energy minimization for nitrobenzene.msf.
Structures created in ChemNote frequently need to be optimized using energy minimization before modeling operations are started.
Display the CHARMm menu and select Minimization Options. In a dialog box containing the minimization setup options, select the option:
Number of Minimization Steps: 100
Coordinate Update Frequency: 5
Energy Gradient Tolerance: 0.001
Energy Value Tolerance: 0.000
Initial Step Size: 0.020
Step Value Tolerance: 0.000
Click the OK button. The dialog box is cleared from the screen and new minimization parameters are established.
4. Start minimization for nitrobenzene.msf.
From the Modeling palette, select CHARMm Minimization. As the CHARMm calculation begins, the cursor changes from an arrow to a watch. The message line displays information regarding the progress of the minimization process, which is completed when the watch is restored to an arrow.
The minimized energy results are displayed in the upper-right corner of the viewing area and in the textport.
5. Save the minimization results.
In the Modeling palette, select Save Changes. A dialog box offers the option to save the new coordinates of nitrobenzene.msf.
Create New Generation of nitrobenzene.msf
Select the OK button and the dialog box is cleared from the screen. The textport indicates that the old structure file is renamed nitrobenzene.msf,001 and the minimized structure is saved in nitrobenzene.msf.
6. Start the Crystal Modeling application.
Display the Applications menu and select Crystal Modeling. From the scrolling list in the Space Group dialog box, select the option:
In the Enter Dimensions for Triclinic Cell dialog box, enter the values:
a: 10
b: 10
c: 10
alpha: 90
beta: 90
gamma: 90
Click the OK button and the Enter Orthogonalization Code dialog box is displayed.
Click the OK button and the Crystal Modeling palette is displayed.
From the Crystal Modeling palette, select Modify Symmetry Copies and the Symmetry Copies palette is displayed.
Select Add LxMxN Box. In the Enter Box Dimensions dialog box, enter the values:
from to
l -1 1
m -1 1
n -1 1
Click the OK button. The 26 symmetry copies are created and displayed in the cubic volume.
Click the Reset View button in the Dial Emulator palette and apply global rotations so that all copies can be seen.
From the Symmetry Copies palette, select Exit Symmetry Copies and the palette is removed from the screen.
From the Crystal Modeling palette, select Symmetry Mode. Each symmetry copy is converted from structures with real atoms to images that are graphical objects. The Minimize Crystal selection is also enabled.
From the Crystal Modeling palette, select Minimize Crystal. The lattice parameters are optimized along with the molecule in the crystal environment. Save and Reject are enabled.
From the palette, select Save and the new coordinates are saved in nitrobenzene.msf
From the Crystal Modeling palette, select Exit Crystal Builder. A dialog box asks if copies are to be retained.
Click the OK button. The copies are deleted and the Modeling palette is redisplayed.
The QUANTA Applications menu contains optional protein applications:
Protein Design is an application for manipulating and analyzing protein structures. It uses and extends the molecular graphics capabilities of QUANTA and its interface to CHARMm for proteins.
Protein MODELER is an automated protein homology package that builds a 3D model for a protein sequence using data from the alignment of the sequence with one or more homologous proteins.
Protein Design includes tools for predicting secondary and tertiary structure, alignment, superimposition, homology, and protein modeling. It can only be accessed from the Application menu and activates two palettes, Protein Design and Protein Utilities.
The Protein Health application provides tools for qualitative analysis of protein structures. With this application, you may examine the quality of structural parameters, such as backbone and sidechain conformation and overall molecular packing, to visually determine nonstandard areas or conditions in the molecule.
Protein Health is packaged with Protein Design or may be used in combination with the X-Ray or NMR applications. It can be accessed from the Applications menu or from within Protein Design.
The Protein Profile Analysis application characterizes the environment around each residue in a protein structure to generate a protein profile. The profile, composed of a matrix of characteristics, can be used to compare protein structures globally and locally and to evaluate the quality of a generated homology model.
Protein Profile Analysis can be accessed from the Applications menu or from within Protein Design.
Documentation of the protein applications is available in the Protein User's Guide and the Protein Reference.
The X-Ray applications X-AUTOFIT, X-BUILD, X-POWERFIT,X-LIGAND and X-SOLVATE provide tools for building the 3D coordinates of proteins and nucleic acids into electron density. The interfaces to CNX and X-PLOR facilitate structure refinement.
The X-AUTOFIT application provides tools to trace Ca coordinates into electron density as part of the de novo process of X-Ray structure determination. The application provides semi-automated tools to build Ca atoms using "bones" skeletonization of the electron density. Sequence assignment using fuzzy logic and three automated methods to convert the Ca trace into all-atom models are provided.
The X-POWERFIT application provides automated methods for tracing Ca coordinates into electron density maps and represents a rapid method for map interpretation.
X-BUILD provides tools for building all-atom models into electron density. These include three types of real-space torsion angle refinement (rigid-body refinement, loop fitting, and regularization) and several manual tools for model building.
X-LIGAND is an application for the automated fitting of complex ligands into omit/difference electron densities, including conformational searching of flexible ligands.
X-SOLVATE provides an automated method for water fitting into electron density.
The interfaces to CNX and X-PLOR allow refinement of crystal structures using both crystallographic data and intramolecular and crystal interactions.
Documentation of the X-Ray applications is available in X-Ray Structure Analysis.
The NMR Structure Determination application provides tools to build and refine 3D molecular models from NMR data. This application features an interactive link between spectrum and structure. It also features interfaces to CNX and X-PLOR for structure calculation and refinement, including distance geometry, simulated annealing, restrained molecular dynamics, energy minimization, NOESY back calculation, and relaxation matrix analysis. NMR Structure Determination provides a complete set of graphical and statistical tools for evaluation of the quality of structures.
Crystal Modeling generates and modifies structures based on translational periodicity or crystallographic symmetry. The applications can build periodic or crystalline structures from proteins, polymer segments, biopolymer segments, and small molecules. Symmetry information can be sent to CHARMm, and additional investigations can be performed in other QUANTA applications.
The Protein applications are used to manipulate, analyze, and evaluate protein structures. They may be used together or individually with other building and refining applications.
The X-Ray applications provide tools to build and refine 3D molecular models from X-Ray crystallographic data.
The NMR Structure Determination application provides tools to build and refine 3D molecular models from NMR data.
