| FDiscover |
The Constraint, Parameters, Run, and Pseudo_Atom pulldowns contain commands that you use to set up and run an FDiscover job. After you execute these commands, the results can be viewed using commands available in Insight.
As with all commands in Insight, each Discover command has equivalent typed and pulldown menu forms. Typed commands are issued from the keyboard at the Command: prompt located near the bottom of the Insight window. Typed commands can also be placed in a file that can be executed using the Source_File command in the File pulldown. Commands are typed at the Command: prompt in the format Command Pulldown or Command, as indicated by the title at the top of the corresponding parameter block. (However, for documentation purposes, the format is Pulldown/Command, since that is the order in which items are selected when using the mouse.)
When you use FDiscover in the Insight environment:
Outline of using FDiscover within Insight
Most Discover calculations consist of three main steps:
The Potentials command is used to check and modify the potential types. If an error message appears stating, for instance, that open or undefined valences exist, commands in the Modify pulldown (which is accessed from the Biopolymer or Builder module) are used to change bond orders or add hydrogens or to respond to any other error messages before trying again to fix potentials.
The Potentials command is also used for setting the partial charges. Insight assigns partial charges to each atom in the model based on bond increments, which are found in the forcefield file.
Minimization is specified with the Run_Minimization option of the Run/Run command, which is the default calculation type. The minimization algorithm and other parameters are controlled with the Parameters/Minimize command. This command provides a choice of several types of minimizers, each suited for somewhat different situations.
Which algorithm to use depends on two factors--the size of the model and its current state of optimization. Until the derivatives are well below 100 kcal mol-1 Å-1, it is likely that the structure is outside the quadratic region of the potential energy surface. Algorithms that assume the energy surface to be quadratic (Newton-Raphson, VA09A [BFGS], and conjugate gradients) can be unstable in this situation. Therefore, as a general rule, steepest descents is often the best minimizer to use for the first 10-100 steps, after which conjugate gradients or a Newton-Raphson minimizer can be used to complete the minimization to convergence.
Other options in the Parameters/Minimize command include specification of the convergence criteria, such as the number of Iterations or the maximum Derivative desired. Note that the default operation is to perform a steepest-descents minimization for 100 iterations or until the rms derivative falls below 0.05 kcal mol-1 Å-1, whichever occurs first.
The Charges option can be included in the calculation if charges have been properly assigned. If Charges is turned off, Coulombic interactions are not included in the potential energy expression.
The Cross option means to include cross terms in the calculation when the CVFF forcefields are used and has no effect when other forcefields are used. The cross terms represent couplings between deformations of internal coordinates. For example, the CVFF forcefield includes a term representing the coupling between adjacent bonds--a bond-bond term--as well as a term describing the interaction between an angle and the bond forming one side of the angle--a bond-angle term. Such cross terms are important for accurately reproducing experimental properties such as vibrational frequencies, but can cause problems during the initial refinement of highly distorted structures. Therefore, when starting with a poor initial structure (derivatives > 100 mol-1 Å-1), you should use 10-100 steps of steepest-descents minimization without cross terms or Morse bond terms, to correct the major distortions. Once the structure is reasonable, you may then include cross terms, use Morse bond terms, and switch to other, more rapidly convergent minimizers.
The Morse option is used to specify the use of a Morse potential for bond stretching rather than the default harmonic potential, when CVFF is used. For other forcefields this option has no effect. The Morse potential is a better approximation of the true bond-stretching potential, but it can lead to computational problems for unoptimized structures having very short (< 0.5 Å) or very long (> 3 Å) bonds. Therefore, as with cross terms, the Morse potential should be used only with reasonably optimized structures.
A dynamics run has two distinct phases: the initialization or equilibration phase and the resume or data-collection phase. During initialization, the model is raised to and equilibrated at the target temperature. During the resume phase, the temperature is constant and data are collected for analysis.
Dynamics is set up using the Parameters/Dynamics command. Options in this command let you specify Equilibration (to define how many iterations are used to reach and equilibrate at the target temperature) and Steps (to define how many iterations are performed once the temperature is achieved). Increasing the default Time Step of 1 fs (the time interval between each iteration) is not recommended, although in very-high-temperature dynamics, it may be necessary to shorten the Time Step to prevent breakdown of the numerical integration, which would cause the run to stop due to a sudden large increase in the energy of the model.
The Charges, Cross, and Morse options (described under Minimization) can be turned on or off for a dynamics run.
Using constraints and restraints
The Constraint pulldown contains commands for tailoring the energy calculation to fit specific needs. The Constraint/Fix command freezes specified atoms at their initial location for the duration of a calculation. Not only is this useful for the obvious purpose of keeping some atoms fixed, but fixing atoms can often cut computational costs significantly. The calculated absolute energy is arbitrary, depending on the forcefield and the model topology. Only relative energies of models with the same number of bonds, etc. are meaningful. Because the terms for energies between fixed atoms sum to a constant, which cancel in any relative-energy calculation, Discover ignores all terms between fixed atoms. If you are working with a large model but are interested in only a small part of it, you might fix all the atoms or residues not involved with the interesting part. The moving atoms still feel the effect of the fixed atoms--the bonds, angles, etc., as well as the van der Waals and Coulombic interactions, are still accounted for. However, if 80% of the atoms are fixed the calculation is about 5 times faster.
Other parameters
Details of the calculation of nonbond interactions--the van der Waals and Coulombic interactions--are controlled by the Parameters/Set and Parameters/Variables commands. The Set command allows you to control the value of the dielectric constant used for the Coulombic interactions, as well as to switch the form to a distance-dependent dielectric "constant" if desired. The Variables command gives access to the variables controlling the nonbond list. For large systems it becomes impractical to include all pairwise nonbond interactions--there are simply too many. Discover allows you to truncate the nonbond interactions at a cutoff distance specified in the Variables command. The Variables command controls the temperature and pressure baths used for constant-temperature and constant-pressure dynamics.
Analyzing the results
Insight provides many commands that are useful for analyzing structural aspects of a model, such as distances and angles, for comparing models using rms matching, etc. whether the models are the results of a Discover calculation or created in some other fashion. Although it is beyond the scope of this section to describe these commands, some comments about Insight features particularly related to Discover are presented here. Please refer to the Insight documentation for more details.