8.2 AMMP calculation

AMMP is a modern full-featured molecular mechanics, dynamics and modelling program. It can manipulate both small molecules and macromolecules including proteins, nucleic acids and other polymers. In addition to standard features, like numerically stable molecular dynamics, fast multipole method for including all atoms in the calculation of long range potentials and robust structural optimizers, it has a flexible choice of potentials and a simple yet powerful ability to manipulate molecules and analyze individual energy terms. One major advantage over many other programs is that it is easy to introduce non-standard polymer linkages, unusual ligands or non-standard residues. Adding missing hydrogen atoms and completing partial structures, which are difficult for many programs, are straightforward in AMMP. For more information, see the AMMP manual.

Selecting an item in the Calculate Ammp menu, the AMMP dialog windows is shown. At this time, it's possible to do energy minimization and conformational search only, but other calculation modes are accessible trough the AMMP direct commands (see the AMMP manual).
Please remember that before to perform an AMMP calculation, the atom charges must be assigned (for more information, click here). The atom types don't need to be assigned, because they are automatically recognized every time that a calculation starts. If you find problems in the automatic assignment, you can proceed to fix them assigning the atom types using the Calculate Charge & Pot. menu item (SP4 force field) or the manual function (Edit Change Atom/Residue/Chain).

WARNING:

the SP4 force field is atom-oriented: it means that the force constants are computed starting from the atoms parameters and they aren't in angle, bond, torsion and improper tables. To compute that constants, the bond order is required. Optimizations of molecules with wrong bond types (single, partial double, double and triple) could carry out to bad structures. If you need to fix the bond types, select Edit Change Bonds in the menu bar, choose Find the bond types and finally click the Apply button (for more details, click here).
The bond types are automatically checked before starting the minimization. If a problem is found, a warning dialog window is shown by which it's possible to ignore the problem or to abort the procedure highlighting the atoms with the possible wrong bond order.

8.2.1 Energy minimization

To perform an energy minimization, select Minimization in Calculate Ammp menu.

 In the Minimization tab, you can change the main minimization parameters and the minimization algorithm: Single point, Steepest descent, Trust, Conjugate gradients, Quasi-Newton, Truncated Newton, Genetic algorithm, Polytope simplex and Rigid-body. The Graphic update field sets the number of iterations after which the VEGA ZZ 3D view is refreshed (nupdat variable).
When you start the minimization clicking the Run button, the calculation steps and the error messages are shown in VEGA ZZ console. If you want to stop the interactive run, you must click with the right mouse button on the workspace area and select Stop calculation. In the same way, it's possible to shutdown the system when the calculation is finished, checking Power off the system.
Is it possible to save the Trajectory, the Output messages generated by AMMP and shown in the console, the Energy for each trajectory frame and the Velocities (this option isn't yet available), enabling the each field clicking the checkbox. To change the file names and the file formats, click the disk button .

If you are changing the trajectory file name, the Save trajectory file requester is shown, in which you can select the trajectory file format (for more information click here). To copy the file name to all fields, click the small button at the left of the disk button. To revert to the default parameters, click the Default button.

WARNING:

the fields of output files are automatically filled using the file path of the last loaded molecule and the name of the current workspace. If you change the current workspace, the file names are updated and manual changes are lost.

8.2.2 AMMP conformational search

To perform a conformational search, select Conformational search in Calculate Ammp menu.

In Search parameters, you can select the search method (Method combo-box): Systematic, Random and Boltzmann jump.
As first step, you must select the torsion (dihedral) angles that will be considered during the conformational search. To do it, press the Edit torsions button: the Selection tool dialog window will be shown. You can also load the selection by drag & drop of a file or by context menu (Open menu item). By this tool, you can choose all or flexible or user defined torsions and the list is automatically updated in the conformational search windows also. For each torsion, the name (Torsion), the starting value in degrees (Base), the number of rotation steps for the systematic search (Steps) and the range in degrees in which the random rotations are computed (Window) or ending rotation value (End) when you perform the systematic search. The checkbox at the beginning of each line allows to consider or not the torsion in the calculation. With the context menu, you can un/check all torsions (Check all, Uncheck all), un/check the highlighted/selected torsions (Check selected, Uncheck selected) and un/select all torsions (Select all, Unselect all). Highlighting one or more torsions in the list, you can change the parameters (Base, Steps and Window) in the Torsion parameters box. Not all parameter fields are enabled at the same time and that's related to the type of the search that you selected (see Method combo-box).
Checking Minimize all conformations, a conjugate gradients minimization is performed for each generated conformation. You can set the number of minimization steps (Steps) and toler value (Toler). Generally it's strongly recommended to enable this option.
Choosing the random search method, the Steps field in the Search parameters box is enabled, in which you can specify the number of random conformations that will be generated. In the Apply to box, you can decide to apply the random rotation to the starting conformation (none checked), to the previous generated conformation (Previous checked) and to the previous minimized conformation (Previous and Minimized checked). If Minimize all conformations is not checked, the meaning of this last option is the same of Previous checked only.
Choosing the Boltzmann jump method, the Steps, Temp. and RMSD fields are enabled: Steps allows to specify the number of conformations that will be generated, Temp. is the temperature in Kelvin and RMSD is the torsion root mean square difference (in degrees) used in the Boltzmann jump perturbation phase to generate a significant different conformation compared to the previous one.
Clicking the Run button, the conformational search begins and at the end the lowest energy structure is kept in the workspace.

Some operations, shown in the next table, can be done by the context menu that can be displayed by clicking with the right mouse button on the torsion list:

WARNING:

it's strongly recommended to set the Graphic update to 1, otherwise not all conformations are saved in the output file, but only one every N conformations, where N is the graphic update value.

8.2.2.1 Conformational search example

Imagine to perform a conformational search of a small molecule using the Boltzmann jump method:

• Open or build the molecule. If you want use the SP4 force field (recommended), check if the bond types (bond order) are correctly assigned. If it's not true, select Edit Change Bonds in the main menu, choose Find the bond types, click Apply.

• Fix the atom types (optional) and the charges (Calculate Charge & Pot.).

• If the starting geometry isn't minimized, before the conformational search, perform a full minimization. To do it, open the minimization dialog window (Calculate Ammp Minimization), uncheck the outputs (Trajectory, Output and Energy), select Conjugate gradients, 3000 steps, 0.01 toler, 0 steepest steps and finally click the Run button.

• Open the conformational search dialog window (Calculate Ammp Conformational search).

• Add all flexible torsions clicking the Edit torsion buttons. For more information about the selection tool click here.

• In the Search parameters box, set Method = Boltzmann jump, Steps = 1000 (default value), Temp. = 1000 and RMSD = 60 (default value).

• Check Minimize all conformations, Steps = 50, Toler = 0.01 (default value).

• Check Trajectory, Output and Energy outputs. Change the default file name and or the trajectory format if it's required by you.

• Click the Run button.

• At the end of the calculation, three files will be obtained: a trajectory file (the trajectory analysis tool can open it), an output file containing all messages printed in the console by AMMP and an energy file in CSV format (the first value is the conformation number and the second one is the energy).

• The resulting conformations can be finally clustered (see Trajectory analysis).

8.2.3 AMMP console

In the Console tab, it's possible to control AMMP sending direct commands.

This function is useful to perform operations not implemented in the graphic user interface or to get/set the system variables. The output is always redirected to VEGA ZZ console.
The commands must be typed in the bottom box and confirmed clicking Send or pressing the return key. The top box is the command history containing the latest typed commands. They can be repeated double clicking the line.

8.2.4 Calculation parameters

The Parameters tab allows to change the Dielectric constant (dielect variable), the Long range cutoff (cutoff variable), the Short range cutoff (mxcut variable), the Update full electrostatic threshold (mxdq variable), the Lambda value for homotopic force field terms (lambda variable) and Random number seed (seed variable). This value is used to initialize the pseudo-random number generator.

In Constraints box, it's possible to enable the use of the constraints defined by the Atom constraints function: None makes all atoms free without constraints,  Atom fixing keep the atoms totally fixed (see ACTIVE and INACTIVE commands) and Tethering allows little movements around the starting position of the atoms depending on force constants (see TETHER command).
To revert to default parameters, click the Default button.

8.2.5 Potential terms

In Potential tab, it's possible to change the potential terms used for the energy evaluation.

For more details, see the AMMP's USE command. In the Force field box, you can change the force field type used by AMMP: SP4 (the standard AMMP force field) and CHARMM 22. The Template button allows to change the ATDL template used for the atom type recognition, the Parameters button allows to change the potential parameters. To revert to default parameters, click the Default button.

8.2.5.1 Non-SP4 force fields

The parameter files of these force fields must be in the standard CHARMM/NAMD format. They must placed in the VEGA ZZ\Data and in the VEGA ZZ\Data\Parameters directories and they must have the .inp extension. For the automatic atom type assignment, for each .inp file must exist a .tem file containing the ATDL tremplate (e.g. CHARMM22_PROT.inp and CHARMM22_PROT.tem). The parameter files interpreter included in the HyperDrive library has the pre-processor feature to include more files:

*
* CHARMM 22 parameters file for VEGA ZZ
*
INCLUDE "Parameters/par_all22_lipid.inp"
INCLUDE "Parameters/par_all22_na.inp"
INCLUDE "Parameters/par_all22_prot.inp"
INCLUDE "Parameters/par_all22_vega.inp"
INCLUDE "Parameters/par_all22_user.inp"

WARNING:

no error message is shown if the included file doesn't exist. In the VEGA ZZ\Data\Parameters directory, custom parameter files can be placed: *_vega.inp are created by the VEGA team to expand the standard parameters and *_user.inp can be generated by users when the parameters are missing in the standard files.
When a non-SP4 force field is selected, is it possible that one or more parameters are missing and so the missing parameter table is shown in order to allow to the user to add the missing parameter.

8.2.6 Hosts

AMMP can be executed on local and remote hosts according to the VEGA ZZ calculation host concept (for more information, click here).

If you select a local host, the calculation is executed using the local hardware, otherwise is executed on a remote host. Host pools allows to filter the host list and the default pools are: All hosts, Local hosts and Remote hosts. Other polls can be defined by the user for massive parallel calculations not yet implemented.
Selecting Localhost the calculation is immediately executed in interactive mode (if you close VEGA ZZ, the job is stopped); selecting Localhost background, the calculation is started in background and it can't be controlled by VEGA ZZ (if you close VEGA ZZ, the job continues without stopping itself); selecting Localhost save file, the calculation is not started and the input file is created to run the job later.
Please note the duplicated hosts: they are child hosts and they are assigned one for each physical or virtual CPU (for more information, click here).
The Edit button allows to open the host configuration window.