Construction

Several tools are available to construct molecular models. The simplest tool is the Add command in the File menu, which makes it possible to generate a model from fragments stored in different files. Executing this command starts the preview of the added molecule(s). The initial model can be shifted or rotated and the added molecules overlapping with the model atoms can be removed. An example of this is given in A Typical Simulation Session in the Getting Started section and described in the Menu Commands > File operations > Add section. More complex construction operations are described below. The current program version supports:

Sequence editor

Sequence editor is the main tool to generate molecular models. It allows chain molecules to be constructed from predefined residues. Clearly, this construction mode is not universal. A required residue can be missing in the database or the constructed molecule can be not polymeric. Nevertheless, we believe that it is the principal construction mode due to two reasons. First, it corresponds to the requirements of scientists studying biological molecules. Proteins and nucleic acids are large chain structures. Due to their size, regular structure, and scientific importance, they require special construction tools.

Second, our constructor is oriented towards developing molecular mechanics models. Hence, we need a tool to associate each atom with its molecular mechanics type as well as with the partial charge corresponding to the selected force field. Such association is a nontrivial task for large models. Some systems make the association by automatically defining the type of each atom according to its environment. From the user's viewpoint, it is a very convenient way. Unfortunately, correct working of such programs can hardly be guaranteed. The rules for type definition from the environmental atoms are complex and many such rules are required. Type definition error is hard to identify in a large model. We believe that explicit definition of types and charges for each force field provides for the most reliable associations. Such association presets are stored in special files (\Repository folder). Unfortunately, this technique also cannot guarantee the correct working considering a great data volume to be entered; still, it is more reliable.

Sequence editor can be invoked from the Edit > Sequence menu or by pressing the toolbar button . It appears in the lower panel.

The figure shows the Sequence editor panel in demonstration mode. The buttons with residues hold the central position. The list of molecules is shown in the upper part of the panel. The molecules not composed of residues are not listed.

The left part of the panel is intended to control the model construction. New molecules can be created, residues can be appended to the available molecules, and the automatic or sequence entry modes can be triggered. If the Auto option is unchecked, pressing a residue button does not add the residue to the model. Instead, its name is added to the sequence text string, which is converted to a model after pressing the Apply button. In addition to pressing the residue buttons, the sequence string can be entered using keyboard or copied from a different program. Two alternative residue codes can be used, e.g., one-letter or three-letter codes for amino acids. Codes can be selected using the Alias button to the right of the sequence string.

The residue class can be selected in the window to the left of the residue buttons. Clicking on the desired class brings a set of buttons with the corresponding residues. The classes are arranged in a hierarchy of folders just as files on a PC. Double-clicking a folder name opens it, while double-clicking the “..” sign brings the user to the upper-level folder. Actually, these are subfolders in the Repository folder. Editing it allows the user to create individual sets of residues and conformational prototypes of chain molecules as described in the description of the Edit > Sequence menu.

The Conformational type window can be found to the right of the residue buttons. The conformational type is defined by a set of parameters including the torsion angles (shown in the rightmost window). These parameters can be applied to each added residue or there may be sets of parameters applied to a sequence of added residues. For instance, the ‘beta turn II’ conformational type includes individual sets of parameters applied to each first, second, third, and fourth residue. The current step is highlighted and its parameters are shown in the rightmost window (Geometry parameters). The current step can be selected by double-clicking in the right lower window.

Let us construct several chain molecules.

Example 1. Trans-gauche-trans hexane

Opening the Sequence editor window brings you to the demonstration panel. Several residues that can be used to build simple molecules are shown. Let us press the –CH2– button. A propane molecule appears rather than methylene. The constructor is designed not to generate molecules with dangling bonds; instead, it generates a molecule composed of the desired residue with stub residues. The methyl group is commonly used as a stub residue. Accordingly, the methylene residue is presented in the Sequence editor window as propane: methylene with two methyl stubs (Me–CH2–Me).

Pressing the –CH2– button once more yields a butane, i.e., the molecule was extended by a methylene group as follows:

• a second propane molecule is generated:
  Me–CH₂–Me + Me–CH₂–Me;

• the molecules are arranged in space so that the stub bonds match each other as close as possible;

• the second and first stubs are removed in the first and second propane molecules, respectively, and a chemical bond is created between the molecules:
  Me–CH₂– + –CH₂–Me → Me–CH₂–CH₂–Me;

• the torsion angle of the new bond is set equal to 180°. If the Joint parameter was defined in the Geometry parameters window, the torsion angle is set equal to it.

Since no conformation type was chosen, this yielded a trans-butane (with a torsion angle of 180°).

Let us append another methylene group in a gauche conformation. Select gauche as the Conformational type and press the –CH2– button once more. Select ‘– default –’ as the Conformational type and press the –CH2– button to add another methylene group in a trans conformation. This yields a hexane molecule in a trans-gauche-trans conformation.

Comment on Force Field Association

The introduction of stub atoms in residues seeing as methyl groups and using them in assembly of chain molecules following the Me–CH₂–Me + Me–CH₂–Me mechanism is significant not only to avoid molecules with dangling bonds. The problem of molecular mechanics types associated with atoms is more important. A molecule assembled is already associated with a certain force field. The associated force field can be checked in the information window . It looks like butane can be assembled from four methane molecules (CH₄ + CH₄ + CH₄ + CH₄) or from two ethane molecules (C₂H₆ + C₂H₆). However, what will be the atom type definition procedure in this case considering that methane and ethane have unique parameterization in some force fields? Butane molecule assembled from methane fragments would inherit wrong atom types.

This problem is considered in detail in the Force Field Association section.

Example 2. Alpha-helix

Let us assemble a biomolecule fragment with a desired secondary structure. Protein α-helix is the simplest example. Let us assemble it from alanine residues:

• select the Amino Acids section, which opens a window with 20 amino acids;

• select Alpha helix as the Conformational type. The angles φ = –57.8° and ψ = –47° typical of α-helix appear in the Geometry parameters window;

• press the Ala button several times. A helical structure with typical hydrogen bonds appears:

Example 3. Beta-sheet

Let us now assemble a more complex structure of a β-sheet. It includes extended regions folded into a sheet due to type II β-turns. We will assemble a β-sheet from fragments including four amino acids for both the strand and turns.