Molecular dynamics analysis (ANATRA)

Introduction.

The ANATRA menu holds a set of options that allow you to analyse GROMOS molecular dynamics trajectories. Since GROMOS does not use IUPAC nomenclature and a non-IUPAC atom order, some synchronisation between the WHAT IF soup and the GROMOS files needs to be done. You will therefore often be prompted for the name of a GROMOS coordinate file and the corresponding molecule in the soup. WHAT IF will align these two at the atomic level, and use this alignment when reading the trajectory file. It is therefore of utmost importance that you keep the corresponding trajectory and coordinate file together.

The way to analyse the trajectory is chosen by the user, but WHAT IF requires a certain input. WHAT IF needs a GROMOS coordinate file (containing also atom names etc.) named WEDAVPGRO10.DAT and a trajectory file WEDFITCRD10.DAT. These are files produced by the program WEDTRA, and if these files are not present in the the directory from which WHAT IF is run, WHAT IF will ask for the 'raw' GROMOS output and run WEDTRA to create these files. Once WEDTRA has been run, the user can select from a dozen or so options representing properties that can be followed during the trajectory.

Large parts of the analysis software are written by B. de Groot (B.B-tje).

Graphical trajectory analysis

Make a trajectory movie (TRAGRA)

The command TRAGRA will like most ANATRA options prompt you for: A GROMOS file name; The number of the corrsponding molecule in the soup; a trajectory file name and the number of trajectory steps to skip between the trajectory steps that should be used; The number of initial trajectory steps to be skipped (the so-called warm-up phase).

You will be prompted for the residues to be followed, and this subset of residues will be put in the movie option. Be aware that only 100 steps can be displayed at once.

Dispaly a trajectory (TRAGRL)

The command TRAGRL will like most ANATRA options prompt you for: A GROMOS file name; The number of the corrsponding molecule in the soup; a trajectory file name and the number of trajectory steps to skip between the trajectory steps that should be used; The number of initial trajectory steps to be skipped (the so-called warm-up phase).

You will be prompted for the residues to be followed, and this subset of residues will be extracted from all selected trajectory steps, and put in a mol-item.

Make a centered trajectory movie (TRACEN)

The command TRACEN will like most ANATRA options prompt you for: A GROMOS file name; The number of the corrsponding molecule in the soup; a trajectory file name and the number of trajectory steps to skip between the trajectory steps that should be used; The number of initial trajectory steps to be skipped (the so-called warm-up phase).

You will be prompted for the residues to be followed, and this subset of residues will be put in the movie option. You will also be prompted for the atom on which to center the movie. All trajectories will be translated such that this atom stays at the same spot. Be aware that only 100 steps can be displayed at once.

Follow atoms through a trajectory (FOLLOW)

The command FOLLOW will like most ANATRA options prompt you for: A GROMOS file name; The number of the corrsponding molecule in the soup; a trajectory file name and the number of trajectory steps to skip between the trajectory steps that should be used; The number of initial trajectory steps to be skipped (the so-called warm-up phase).

FOLLOW will follow the active atoms (see the USE*** commands) through a trajectory file. Lines will be drawn that connect the subsequent positions of these atoms in space. These lines will be put in a mol-item.

Make a trajectory movie (TRASPH)

The command TRAGRA will like most ANATRA options prompt you for: A GROMOS file name; The number of the corrsponding molecule in the soup; a trajectory file name and the number of trajectory steps to skip between the trajectory steps that should be used; The number of initial trajectory steps to be skipped (the so-called warm-up phase).

You will be prompted for a residue and for the radius of the sphere around this residue. This sphere of residues will be followed through the trajectory and be put in the movie option. Be aware that only 100 steps can be displayed per movie.

Movie of hydrogen bonds in sphere (TRAHBO)

The command TRAHBO will like most ANATRA options prompt you for: A GROMOS file name; The number of the corrsponding molecule in the soup; a trajectory file name and the number of trajectory steps to skip between the trajectory steps that should be used; The number of initial trajectory steps to be skipped (the so-called warm-up phase).

You will be prompted for a residue and for the radius of the sphere around this residue. All Hydrogen bonds within this sphere of residues will be followed through the trajectory and be put in the movie option. Be aware that only 100 steps can be displayed per movie.

Follow one atom through trajectory (TRA1AT)

The command TRAGRA will like most ANATRA options prompt you for: A GROMOS file name; The number of the corrsponding molecule in the soup; a trajectory file name and the number of trajectory steps to skip between the trajectory steps that should be used; The number of initial trajectory steps to be skipped (the so-called warm-up phase).

You will be prompted for one atom. This atom will be followed through the trajectory and its trajectory will be put in a MOL-item.

Looping automatically through a movie (LOOPER)

The command LOOPER will prompt you for the number of frames (should not be larger than the number you sent to the screen with an earlier TRA-like option). You will also be prompted for a mode, cyclic or oscillating. In cyclic mode you see a jump everytime at the end of the movie, because WHAT IF jumps back in one step from the last frame to the first frame again, in oscillating mode the direction of the movie is reversed every time the last or the first frame is reached. Finally you will be prompted for the speed of the movie. This number depends on the size of the movie, the number lines/dots per movie step, and, of course, on your hardware. So, you will have to experiment a bit with the speed. Normally numbers between 1 and 10 are fine.

Activating atoms

The option FOLLOW will follow activated atoms through a trajectory, and put their trajectory traces in a MOL-item. You can use the USE*** options to activate atoms.

Activate all atoms (USEALL)

The command USEALL activates all atoms in the soup for usage by the FOLLOW option.

Activate all alpha carbons (USECA)

The command USECA activates all alpha carbon atoms in the soup for usage by the FOLLOW option.

Parameters (PARAMS)

The command PARAMS will activate the trajectory analysis parameter menu. The following parameters are available:

Pickability flag (PCWHAT)

If you want, atoms can be pickable during a trajectory. Since, however, the number of pickable atoms is limited, you can for long trajectories of large molecules decide to only make the alpha carbons pickable.

If you give 0 only alpha carbons will be pickable; 1 makes all atoms pickable.

Numerical trajectory analysis

Initializing the setup of the anatra menu (WADINI)

The first thing WADINI will ask is if you want to use the grafical interface of WHAT IF or not. Selecting the grafical interface will pop up a graphics screen with your molecule after typing for instance WADDIS. Subsequently, two atoms can be clicked between which the distance will be monitored as a function of time in your trajectory. If the graphical interface was not selected, WADDIS will prompt you for the two atom numbers between which the distance will be monitored.

Typing WADINI in the ANATRA menu will initialize the anatra menu, and check if the files required by ANATRA are in your current directory. If you have performed your simulation with WHAT IF, and did the trajectory handling step WEDTRA from the essdyn menu, these files will be present. If the files can not be found by WHAT IF, you will be asked for the names of the input files required. If some processing still needs to be done, WHAT IF will automaticcaly run WEDTRA to provide the proper files.

ANATRA works as follows: After WADINI has been run, you can select any number out of the options present in the ANATRA menu ( they are saved in a script-like manner). WHAT IF will remember all selected options, and when WADEXE is selected, all trajectory evaluations will be executed. Upon calling WADINI, all previously executed commands will be removed from WHAT IF's memory, which also occurs at calling WADEXE.

The options to choose from are:

Initializing the script (WADISC)

Upon calling WADISC, the script will be initialized.

WADSSC (shoing the script)

WADSSC will cause WHAT IF to show the script containing the options selected so far, with their parameters.

Run the script (WADEXE)

WADEXE will execute all the commands in the script and analyze the results (put the output either to the screen or the printer).

Evaluate the results of a previous run of the script (WADANA)

If you want to visualize the results of (a previous run of) the script (again) you can select WADANA. It will give the same output as WADEXE, only not execute the program to generate the data again.

Using DSSP to evaluate geometrical properties (WADSSP)

WADSSP selects DSSP (if available, i.e. if you have the license, it is not part of the WHAT IF package...) for the calculation of the geometrical properties ACC (total solvent accessible surface), HST (secondary structure assignments), and HBO (the total number of main chain - main chain hydrogen bonds). For the latter two, also DSSP independent options have been written (WADHST and WADHBO). However, note that these options have not been well tested and only provide qualitative data. Therefore we suggest that you only use them for fast experiments (they are considerably faster than DSSP) but not for any quantitative needs.

The result of WADSSP is the creation of four files in your directory. Only the options selected in the script are automatically visualized by WHAT IF after using WADEXE (so, for instance, if your script only contains the commands WADSSP and WADHBO, only the output of HBO (the number of hydrogen bonds) is evaluated after WADEXE. ACC and HST are calculated without any extra cost as well, only not visualized).

Following the secondary structure as a function of time (WADHST)

Depending on the WADSSP flag (see WADSSP) secondary structure assignments during the trajectory will either be calculated by the program DSSP or by an approximation that is less accurate but a lot faster. selecting WADHST will produce two kinds of output:

1) it counts the number of residues in random coil conformation as a function of time

2) it produces a map of all secondary structure as a function of time

Following a inter atomic distance through time (WADDIS)

Depending on the selection in WADINI for the graphical interface, the user will either click two atoms on the screen between which the distance will be monitored in the trajectory or type the atom numbers of the two atoms.

Following an angle through time (WADANG)

Depending on the selection in WADINI for the graphical interface, the user will either click three atoms on the screen between which the angle atom 1 - atom 2 - atom 3 will be monitored in the trajectory or type the atom numbers of the three atoms.

Following a torsion angle through time (WADTRS)

Depending on the selection in WADINI for the graphical interface, the user will either click four atoms on the screen between which the torsion angle atom 1 - atom 2 - atom 3 - atom 4 will be monitored in the trajectory or type the atom numbers of the four atoms.

Following a hydrogen bond through time (WAD1HB)

Depending on the selection in WADINI for the graphical interface, the user will either click three atoms on the screen (donor, hydrogen, acceptor) or type the atom numbers of the three atoms, and WHAT IF will calculate the percentage of time that a hydrogen bond is formed by these three atoms. On the basis of this, WHAT IF will decide if a stable hydrogen bond was present at this position or not. WHAT IF uses the hydrogen-acceptor distance and the donor-hydrogen-acceptor angle to decide whether a hydrogen bond is present or not. It generates a number that is some kind of stability measure for a hydrogen bond. the larger it gets, the more unstable the hydrogen bond is.

Following a phi/psi angle through time (WAD1PP)

Depending on the selection in WADINI for the graphical interface, the user will either click a residue on the screen or type the residue number of the residue of which the phi/psi angles will be monitored. The result is presented in a ramachandran plot, where phi is ranging from -180 - +180 degrees along the x-axis and psi is put along the y-axis.

Following the radius of gyration as a function of time (WADGYR)

Selecting WADGYR will produce a plot of the radius of gyration of the simulated protein as a function of time. It is a measure of the compactness of the protein and it should not increase too much duing your simulation. When it does, this is usuallly a sign of the first stages of unfolding of a protein.

Following backbone-backbone hydrogen bonds as a function of time (WADHBO)

Depending on the WADSSP flag (see WADSSP) hydrogen bonds between backbone atoms are monitored either by DSSP or by an approximation that is less accurate but a lot faster.

Following dihedral angles as a function of time (WADDIH)

WADDIH will count the number of phi/psi combinations per frame in an unfavourable region of the Ramachandran plot as a function of time.

Following solvent accessible surface as a function of time (WADACC)

WADACC evaluates the total solvent accessible surface of each frame as a function of time. Now, WADACC only works in combination with WADSSP. Somewhere in the future, also a DSSP independent (ans faster) calculation of ACC will be available.

Calculating the RMS of positional fluctuations (WADFLC)

WADFLC calculates the rms of the atomic fluctuations of the atoms. This is a very crude measure to find out in which part of the protein the motion is concentrated.

Isolating one frame out of a trajectory (WADGRO)

WADGRO will isolate one frame from the trajectory file and write it away in GROMOS coordinate file format.

Do most of the fast-to-check overall analyses (WADALL)

WADALL automatically executes and evaluates WADDIH, WADHBO, WADHST, WADRMS and WADGYR.

Other options

Change the project number (PROJEC)

GROMOS gives default file names to all its files. To keep them apart, you can add a project number to the options. (You see the two digits in the filenames that contain the project number plus ten added to it). The command PROJEC allows you to (re-)set the project number.

Count the frames in a trajectory (TRACNT)

If you forgot how many steps there are in a trajectory file, you can use the TRACNT option to count them.

Analyse one distance through a trajectory (ANADST)

The command ANADST will like most ANATRA options prompt you for: A GROMOS file name; The number of the corrsponding molecule in the soup; a trajectory file name and the number of trajectory steps to skip between the trajectory steps that should be used; The number of initial trajectory steps to be skipped (the so-called warm-up phase).

Then you will be prompted for two atoms. These two atoms will be followed during the trajectory, and some statistics about their distance will be given.

Analyse atomic volume through a trajectory (ANAVOL)

The command ANAVOL will like most ANATRA options prompt you for: A GROMOS file name; The number of the corrsponding molecule in the soup; a trajectory file name and the number of trajectory steps to skip between the trajectory steps that should be used; The number of initial trajectory steps to be skipped (the so-called warm-up phase).

Then you will be prompted for one atom. Some statistics about the volume occupied by this atom during the trajectory will be given.

Analyse one hydrogen bond through a trajectory (ANAHBO)

The command ANAHBO will like most ANATRA options prompt you for: A GROMOS file name; The number of the corrsponding molecule in the soup; a trajectory file name and the number of trajectory steps to skip between the trajectory steps that should be used; The number of initial trajectory steps to be skipped (the so-called warm-up phase).

Then you will be prompted for two atoms. If there is a hydrogen bond between these two atoms, this hydrogen bond will be followed during the trajectory, and some statistics will be given.

Look at mobility in a trajectory (TRARMS)

The command TRARMS will like most ANATRA options prompt you for: A GROMOS file name; The number of the corrsponding molecule in the soup; a trajectory file name and the number of trajectory steps to skip between the trajectory steps that should be used; The number of initial trajectory steps to be skipped (the so-called warm-up phase).

Throughout the movie the RMS atomic displacement for the atoms in each residue (with respect to the atoms in the soup) will be calculated, and the plot of the RMS displacement as function of the residue number will be put in the movie.

Run a WHAT IF script over a trajectory (TRASCR)

The command TRASCR allows you to run over a trajectory file, and execute a script file on each step. Be aware that not all options can be used in these script files. Also, it seems wise to save your SOUP before starting this option. You might want to try the script file first on just the SOUP, rather than immediately on the entire trajectory file.

Avoid across box atomic bonds (BNDCHK)

Sometimes one atom of a covalently bound pair of atoms can move across the boundary of the box. This will lead to stange long lines that run all across the screen. To avoid this, you can use the BNDCHK option. Be aware, however, that this costs extra CPU time.