Molecular Design

Model generation

Prior to modeling a molecular system, make sure the files describing it and, possibly, the molecular mechanics force field are available. For small models, such files can be manually created. For systems including thousands of atoms, manual production of the files is impractical. Various automatic systems are commonly used in this case. Unfortunately, a universal system corresponding to most tasks is hardly possible. That is why, below we consider specific tasks of molecular model construction and the corresponding specific tools using our graphical programs. The main model construction tools are realized in the Ascalaph Designer module and AGM Build program.

Merging models from several files

Despite the task simplicity, there are several issues that make the program assistance quite valuable.

First, atoms are numbered in many file formats. Their numbering can be consecutive, individual for each molecule, or missing. This introduces the task of renumbering, which is easy for a program and complex for a human.

Second, superposition of atoms should be avoided in model merging. If we want to add many solvent molecules to a current model, the solvent molecules substantially overlapping with the main model molecules can be removed.

Third, it is essential to be able to move models in space relative to each other. Desirably, the intermediate result should be visible on screen.

All our programs support these operations.

Model drawing on screen

It is convenient to draw molecules on screen with a mouse. Such tool is available in the Ascalaph Designer module. However, this highly convenient way to construct small molecules has a serious limitation. The model atoms are not associated with molecular mechanics types, which are required to work with most force fields. One should bear in mind that wrong type association leads to calculation errors that are hard to identify. If a model can be assembled from parts with correct type association, it is highly recommended to take this opportunity. If a model is not intended for molecular mechanics calculations (e.g., it is intended for quantum chemical calculations), free drawing with a mouse becomes practical.

Chain molecule assembly

Most large molecules explored by chemists and biologists are chain structures composed of residues of one or several types. It is recommended to assemble such molecules using the chain builder. It is not just convenient; essentially, the residues manipulated by the builder include atoms with specified molecular mechanics types. Their correct specification is not a trivial task. That is why, generate a model using the chain builder whenever possible. Even if residues required are not available in the library, it can be beneficial to extend the library instead of using the free drawing constructor, considering that the new residue(s) can prove useful later.

Correct assignment of molecular mechanics types of atoms is a very important problem. This makes the chain builder a basic tool to construct molecules.

The chain builder is available in the AGM Build and Ascalaph Designer programs.

Immersion in solvent

Generated models sometimes should be immersed in a box with solvent. Usually, a box with solvent is generated separately and added to the main model. The simplest way to do it is to repeatedly replicate one or several solvent molecules with a spatial shift along the three axes. This gives rise to a crystal-like structure. This structure can be used immediately or, preferably, after a rough molecular dynamics equilibration.

Generation of crystal-like lattices is supported in AGM Build.

Model adjustment

Editing of conformational parameters

AGM Build and AGM View make it possible to measure and edit the distances, angles, and dihedral angles; however, it is more conveniently realized in Ascalaph Designer. Torsion angles can be specified using conformational prototypes (which are used by the chain builder, in particular). The conformational prototypes are a part of the mlm file format, which is the basic format for all our products. After some torsion angles are added to the end of the mlm file, first, the Cartesian coordinates of the atoms are set and then the torsion angles are adjusted. As a result, the atomic coordinates in the model can differ from the specified Cartesian coordinates.

Geometric optimization

After a model is assembled, it nearly always requires to be optimized. Even if the bond lengths and valance angles were correctly specified, most likely there are problems with overlapping atoms. This problem can be solved in a few tens of optimization steps. In the case of model drawing with a mouse, its geometry is very rough and definitely requires optimization.

Small molecules can be conveniently optimized using empirical quantum mechanical methods (e.g., AM1) supported by the Ascalaph Quantum package.

Force fields

Currently, the AMBER94 is the basic force field in the package. The force field parameters are defined in text files in the data/ForceField folder. Ascalaph Quantum can be useful for development of a force field. In particular, the Potential Derived Charges are assigned to atoms after a quantum mechanical calculation of the model electrostatic properties.