FDiscover

1       Introduction

What Is the Discover® program?

Using appropriate methods and strategies, you can study docking interactions such as enzyme-substrate, polymer-polymer, or receptor-ligand interactions. You can also evaluate the multitude of conformations available to a molecule, energy refine a model-built structure, and evaluate configurations or chemical perturbations of a system.

Typical uses of energy minimization include:

• Optimizing initial geometries of molecules constructed from fragments with the Insight^® molecular modeling program.

• Repairing poor geometries occurring at splice points during homology building of protein structures.

• Mapping the energy barriers for geometric distortions and conformational transitions using "torsion forcing" to obtain Ramachandran-type contour plots for proteins or RIS statistical weights for polymers.

• Evaluating whether a molecule can adopt a template conformation consistent with a pharmacophoric or catalytic site model ("template forcing").

• Searching the conformational space of alternative amino acid sidechains in site-specific mutation studies.

• Identifying likely conformational states for highly flexible molecules such as peptides or for flexible regions of macromolecules such as protein loops.

• Producing sets of 3D structures consistent with distance and torsion constraints deduced from NMR experiments (simulated annealing).

• Calculating free energies of binding, including solvation and entropy effects.

• Probing the locations, conformations, and motions of molecules on catalyst surfaces.

• Calculating normal modes of vibration and vibrational frequencies.

• Analyzing intramolecular and intermolecular interactions in terms of residue-residue or molecule-molecule interactions, energy per residue, or interactions within a radius.

• Calculating diffusion coefficients of small molecules in a polymer matrix.

• Calculating thermal expansion coefficients of amorphous polymers.

• Calculating the radial distribution of liquids and amorphous polymers.

• Performing rigid-body rms comparisons between minimized conformations of the same or similar structures or between simulated and experimentally observed structures.

When purchased with the Insight interface, the FDiscover program is accessible as one of the application modules within the Insight package. (For more information on the basic operations, procedures, and functionality of the Insight package, please refer to the Insight documentation.) The functionality in the Discover program is accessed through pulldown menus that contain the commands to set up the input control file for a Discover job. The parameter block for each command provides you with many useful defaults as well as preset strategies, all of which can be easily modified, if necessary, for your particular calculation. References to atoms or residues, such as for defining torsions or for fixing atoms, can be typed in or can be specified by picking the appropriate atom or residue in the displayed structure. You can then start the run while remaining in the Insight environment.

The menus in the Insight interface can also be used to prepare input files for running the FDiscover program in the standalone mode. These input files can be edited to develop more sophisticated simulation strategies or for repetitive calculations better suited to the automatic control of batch queues.

When run as a standalone program, the FDiscover program uses a simple user interface in which you create a command input file that instructs the Discover program what to do.

The command language used in the input file, the Biosym Tool Command Language (BTCL), gives a high level of control over the variables and functions used in a calculation. These functions include logical operators and flow control statements that allow you to control the calculation based on energies, derivatives, distances, angles, forcing potentials, temperature, and user-defined variables. You can also use alternative input files and can print with conditional operators and with formatting to user-defined output files. These functions provide useful decision points for branching from minimization to dynamics, for example, and for archiving and producing results, so that you can develop sophisticated simulation strategies to be performed in a single run without user intervention.

Comparison of FDiscover and CDiscover

For the most part, the two versions are reasonably compatible with each other. They accept the same format for the .car and .mdf files and produce identical .cor, .arc, and .his files during minimization. The energy calculated by the two programs is identical, within the numerical accuracy of the machines. The input files differ--the Biosym Tool Command Language (BTCL) used in CDiscover differs in both detail and philosophy from the DSL (Discover Simulation Language) used in FDiscover.

Starting the FDiscover program

You can also set up and run the FDiscover program independent of the Insight interface. The standalone user interface is activated by typing discover at the operating system command level.

Using this guide

Tutorial describes tutorial lessons on the use of both modes.

Commands and DSL--Standalone Mode documents the language, commands, and parameters that can be used in the input file to run the FDiscover program. (These commands are the same whether the input file is constructed by means of the Insight or standalone modes of FDiscover.)

The generic file formats are documented separately, and the files specific to the Discover program are documented in Files. Utilities contains some information on utilities.

Additional information

In addition to this printed Discover documentation, on-screen help is available within the Insight environment. It is activated by clicking the help icon, which is the button containing a question mark on the side of the Insight window.

The formats of files that are used on more than one MSI product are now documented separately. Files documents files that are specific to the Discover program.

Many tutorials are available electronically--see Tutorial for more information.

Additional information on using the Insight interface is contained in the Insight documentation. Technical information that is mainly of use to programmers and system administrators is contained in the System Guide. Supplemental information that may be of general interest (including additional information on the electronic documentation) is contained in the Release Notes.

Note on documentation of command names

Standalone mode of the FDiscover program