Forcefield Based Simulations

1       Introduction

This Forcefield-Based Simulations documentation is a general guide to all MSI's simulation engines, that is, software products whose computational work is based on a forcefield. These include CHARMm^®, Discover^®, and the Open Force Field^[TM] (OFF) modules, which are run through the molecular modeling programs (i.e., graphical interfaces) shown in Table 1.

Table 1 . Simulation engines¹ within MSI's molecular modeling programs²

Molecular modeling program and release number	Simulation engine
	CHARMm	Discover3	OFF
Cerius2[TM] 4.0		4
Insight® II 4.0.0
Insight® II 97.0
QUANTA®
standalone5

1 See definitions under What are forcefields and simulation engines?. 2 Discover and OFF each offer a choice of several forcefields (see Table 3); the CHARMm program gives access only to the CHARMm forcefield in QUANTA and standalone, only to MMFF in Cerius2, and is used only in specialized modules in Insight II. 3 Discover exists in two versions: one written in FORTRAN (series 2.8.x, 2.9.x and earlier ; referred to as FDiscover) and the other in C (series 3.0, 3.1, 3.0.0, 4.0.0, 95.0, 96.0, 97.0; referred to as CDiscover). CDiscover and FDiscover are specified in this documentation only where the FORTRAN and C Discover programs have different capabilities. FDiscover and CDiscover (in Insight II) are accessed through the Discover and Discover_3 modules, respectively. 4 CDiscover only. 5 CHARMm and Discover can also be run without the assistance of a graphical molecular modeling program.

Who should use this documentation

Prerequisites

You should already be familiar with:

• The system and windowing software on your workstation.

• How to use the particular MSI molecular modeling program that contains the desired simulation engine (Cerius², Insight, and/or QUANTA).

• A licensed copy of Cerius², Insight, and/or QUANTA as well as of the appropriate simulation engine.

• A directory in which you have write permission.

• Optimizing initial geometries of models constructed in a molecular modeling program such as Cerius^2[TM] or Insight^®.

• 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 polymers 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.

• Running diffusion calculations.

• 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.

Simulation "engine" defined

Simulation engines are the computational packages that handle the application of forcefields in minimization, dynamics, and other molecular mechanics simulations. Currently, MSI-supplied simulation engines include CHARMm, Discover, and OFF. (CHARMm is the name for both a simulation engine and for the forcefield included in that engine.)

"Forcefield" and "energy expression" defined

The functional form of the potential energy expression and the entire set of parameters needed to fit the potential energy surface constitute the forcefield (Ermer 1976). The energy expression is the specific equation set up for a particular model and including (or not) any optional terms.

For example, a forcefield would contain bond-stretching parameters for all combinations of atoms for which it was parameterized, as well as a defined, summed functional form for the bond-stretching term. The corresponding energy expression would contain bond-stretching parameters for only those combinations of bonded atoms actually found in the model being studied, as well as the specific bond-stretching terms for the number and types of bonds in that model (see example under Example energy expression for water).

Importance of the forcefield in simulations

It is important to understand that the forcefield--both the functional form and the parameters themselves--represents the single largest approximation in molecular modeling. The quality of the forcefield, its applicability to the model at hand, and its ability to predict the particular properties measured in the simulation directly determine the validity of the results.

Moledular modeling programs

Molecular modeling programs are the graphical user interfaces (UIFs or GUIs) that can be used to prepare models, set up forcefields, and access the simulation engines. Some simulation engines can also be run in standalone mode, that is, outside the graphical molecular modeling program. Molecular modeling programs currently supplied by MSI include Cerius², Insight, and QUANTA.

Using this guide

• Forcefields presents the concept of an energy surface and compares the forcefields available to MSI's simulation engines, including their functional forms and atom types. Different forcefields have been developed specifically for different types of models or computational experiments.

• Preparing the Energy Expression and the Model concerns concepts such as periodic boundary conditions, nonbond interactions, restraints, and constraints. You typically need to refine both the model and the energy expression that you intend to set up, in order to optimize your calculation conditions.

• Minimization includes information on the minimization algorithms that these programs can use; how, in general, to carry out minimization calculations; and the applicability of minimization in energy and vibration calculations.

• Molecular Dynamics covers the dynamics algorithms in these programs, thermodynamic ensembles, control of temperature and pressure, and constraints during dynamics.

• Free Energy presents relative and absolute free energy calculations.

Additional information

Guides are available for every simulation engine and modeling program that MSI provides, including these:

• MSI Forcefield Engines: CDiscover.

• Cerius² Forcefield Engines: OFF.

• MSI Forcefield Engines: FDiscover.

• MSI Forcefield Engines: CHARMm.

• Cerius² Modeling Environment.

• Insight II.

• QUANTA documentation set.

In addition to the task-oriented documentation for each simulation engine, on-screen help is available within the Cerius², Insight, and QUANTA environments. Please see the documentation for the specific program for how to access the help.

Supplemental documentation

Additional information on using the Cerius², Insight, and QUANTA interfaces, including building models and writing scripts for automated running, is contained in their respective guides. Technical information that is mainly of use to programmers and system administrators is contained in installation/administration guides. Supplemental information that may be of general interest (including additional information on the electronic documentation) is contained in release notes.

MSI's website

The URL for the documentation and customer support areas of MSI's website are :

http://www.msi.com/doc/
http://www.msi.com/support/

Typographical conventions

• Terms introduced for the first time are presented in italic type. For example:

Instructions are given to the software via control panels.

• Keywords in the interface are presented in bold type. In addition, slashes (/) are used to separate a menu item from a submenu item. For example:

Select the View/Colors... menu item means to click the View menu item, drag the cursor down the pulldown menu that appears, and release the mouse button over the Colors... item.

• Words you type or enter are presented in bold type. For example:

Enter 0.001 in the Convergence entry box.

• UNIX command dialog and file samples are represented in a typewriter font. For example, the following illustrates a line in a .grf file:

  
        CERIUS Grapher File
  
  

• Words in italic represent variables. For example:

  
        discovery input_file
  
  

In this example, the name of the file from which data are read in replaces input_file.