ESSENTIAL DYNAMICS ANALYSIS (ESSDYN)

Introduction.

The option ESSDYN brings you in the menu from which you can run the essential dynamics analyses. This analyses molecular dynamics trajectories produced by the simulation package GROMOS.

The essential dynamics method (Proteins 17(4), p. 412-425) is able to filter out large correlated motions in the simulated system which occured during the simulation from uninteresting local motions (mostly vibrations).

The method is usually applied in three steps. These steps can be done separately, by calling WEDTRA, WEDEIG and WEDPRJ respectively. At each step, WHAT IF will ask the user a number of questions, after which an input file for the program which contains all input parameters and names of input/output files will appear in an editor on the screen. The user can check if each parameter is correct and when the editor is quit, WHAT IF will run the appropiate program. Output of the three steps can be analysed by calling ANWTRA, ANWEIG and ANWPRJ respectively.

It is also possible to call WEDALL, which will cause WHAT IF to ask only a couple of questions beforehand, and then runs WEDTRA, WEDEIG and WEDPRJ subsequently, after which the results of each step can be analyzed.

Choosing which (protein) atoms to select for the essential dynamics

analysis (WEDSEL). Upon typing WEDSEL, the user can decide which atoms to include from group one (usually protein) in WEDTRA. These are the atoms which are extracted from the GROMOS trajectories and used for fitting. Only the fitted coordinates of these atoms will be stored.

0 = select all atoms
1 = select only alpha carbon atoms
2 = select alpha carbon atoms and geometrical centers of the side chains.
3 = select alpha carbon atoms and terminal atoms of the side chains.
4 = select phi and psi angles for a dihedral space analysis 
    (yet to be implemented) 

NOTE:

There is no side chain on glycine residues, not even an explicit hydrogen in the GROMOS force field. Therefore, for the geometrical center and the terminal atom of the sidechain of a glycine, a virtual position is constructed from the position of the backbone nitrogen, the alpha carbon and the carbonyl carbon atom.

Allowing the user to choose between visual inspection or printing of

the output created (PRNSEL). With PRNSEL, the user can choose whether in the options to visualize the results of the analyses (ANWTRA, ANWEIG, ANWPRJ and WEDALL) the results are sent to the screen or the printer. The PRNSEL paameter can take two values:

0 = don't print plots, only show them on the screen
1 = make ps files and print the plots (using the command in the cconfi.fig 
    file)

Fitting selected atoms of trajectory to a reference frame (WEDTRA).

WEDTRA is usually the first step in an essential dynamics analysis. It builds a trajectory of atoms selected by the user (this is usually a subset of the atoms that were simulated). The frames of the trajectory are superposed by a least squares fit method on a reference frame. Overall translational and rotational motion are removed since only internal motions of the system are interseting to analyse.

When starting WEDTRA, WHAT IF will prompt the user for a couple of things:

-a GROMOS coordinate file.

This file should contain exactly the same number of atoms as the trajectory that is to be analyzed, and is used for checking how many atoms of each kind (e.g. protein(s), ions, drugs,solvent) are present in the system.

-the basic part of the input trajectory filenames.
-the number of the first trajectory file to be analyzed.
-the number of the last trajectory file to be analyzed.

Usually, GROMOS produces a simulation in a number of steps of a few picoseconds. In each step, an output trajectory file is produced. These files will have names which consist of a basic name and a trajectory number.

WARNING:

Be sure that the trajectory number of the file is the last part of the filename! (this is default when you did your simulation with WHAT IF)

The program will inspect if the input trajectory files are compressed or not. If so, the program will automatically uncompress the files before processing. By default, the input trajectory files are compressed after reading.

-the number of frames per trajectory file.
-for each group that WHAT IF found in the coordinate file, it will ask the 
 user whether it should be included in the analysis or not. In case of a 
protein, a further selection can be made using WEDSEL (see above).
-finally, WHAT IF will ask whether periodic boundary conditions were used
 in the simulation.

After this, the input file for the program WEDTRA will appear in an editor on the screen. The user may want to check if all paramaters are correct, and changes can be made if necessary. The input file should in principle be self-explanatory.

NOTE:

By default, WEDTRA uses the GROMOS coordinate file given on line 1 of the input file also as the reference frame. If this is not the structure on which you want to superpose all frames, you should manually alter the WEDTRA input file.

WEDTRA requires the following input:
-a GROMOS coordinate file containing the same number of atoms as the 
 input trajectory.
-a set of formatted GROMOS trajectory files. The name should end with a 
 trjaectory number.

WEDTRA produces the following output:
-a fitted trajectory file (one file, containing all frames)
 (this trajectory can be visualized using the options in the WHAT IF 
 ANATRA menu).
-a GROMOS coordinate file containing the average positions of all selected 
 atoms.
-a file containing the rms deviation of all fitted frames with respect to 
 the reference frame (can be visualized by calling ANWTRA).

Building up a covariance matrix and diagonalizing it (WEDEIG).

WEDEIG builds a covariance matrix from the trajectory built by WEDTRA.

Upon calling WEDEIG, WHAT IF will inspect if WEDTRA has already been run in the same directory. If not, WEDEIG will prompt for the number of atoms in the trajectory file, otherwise WHAT IF will by default take the same number of atoms as were selected in WEDTRA.

After that, if WEDTRA had not been run already, WHAT IF will prompt for the total number of frames in the file containing the fitted trajectory, and for the name of this file.

Like with WEDTRA, the inputfile for WEDEIG will appear in an editor on the screen after these questions have been answered and changes can be made if necessary.

WEDEIG requires the following input:
-a single file containing a formatted GROMOS trajectory file, of which
 the frames are superposed on a single reference structure.

WEDEIG produces the following output:
-a file containing the average positions of the fitted input trajectory
 in GROMOS trajectory format.
-a file containing the eigenvalues of the built covariance matrix.
 (this file can be visualized by calling ANWEIG).
-a file containing the eigenvectors of the built covariance matrix.
 (a file containing any selected eigenvector can be produced and visualized 
 by calling ANWEIG).
-a file containing the eigenvalues in a cumulative, normalized way.
 (this file can be visualized by calling ANWEIG).

Make projections of trajectory on eigenvectors etc (WEDPRJ).

WEDPRJ will make projections on single eigenvectors of your input fitted trajectory and it will translate the projections onto the first six eigenvectors into cartesian space (GROMOS trajectory file format). It will also produce files containing cartesian coordinates of the system for the minimum and maximum projection onto the first six eigenvectors. Additionally, it will also inspect the distribution of the motion along the first 100 eigenvectors (if there are that many) and compare this distribution with a perfect Gaussian distribution with the same mean and standard deviation. Correlation coefficients are calculated between both types of distributions.

WHAT IF will try to deduce information about the system to be analyzed from the previous steps you took (for instance running WEDTRA or WEDEIG) to prevent having to ask the same questions again. If no history is available, properties like the number of atoms in the system, the number of frames in the input file will have to be provided by the user.

Like with WEDTRA and WEDEIG, an input file for WEDPRJ will appear in an editor on the screen and changes can be made if necessary. At the end of this file, the indices of the eigenvectors onto which projections should be made are listed. WHAT IF will by default put the first ten, the twentieth, the fiftieth and the hundredth eigenvector in this list. If another selection is wanted, the list can be altered in the editor.

WEDPRJ requires the following input:
-a GROMOS coordinate file containing information about the system that is 
 analyzed. It is suggested that the output average position file produced
 by WEDTRA is taken.
-a file containing eigenvectors (output of WEDEIG).
-a file containing the average positions (GROMOS trajectory file format)
 of the atoms in the input trajectory (output of WEDEIG).
-a file containing the input trajectory (GROMOS formatted trajectory file
 format) of which the frames will be projected onto selected eigenvectors.
-a file containing eigenvalues (output of WEDEIG).

WEDPRJ produces the following output:
-files containing projections onto selected eigenvectors
 (these can be visualized by calling ANWPRJ).
-files containing trajectories (GROMOS formatted trajectory format)
 of the motion along the first six eigenvectors (these trajectories
 can be visualized by using the options in the WHAT IF ANATRA menu).
-files containing the coordinates (GROMOS coordinate file format)
 of the minimum and maximum projections onto the first six eigenvectors
 translated into cartesian space (these files can be visualized by WHAT IF).
-a file containing correlation coefficients between the distributions of
 the projections of the input trajectory onto the first 100 eigenvectors
 and the corresponding ideal Gaussian distributions (this file can be 
 visualized by calling ANWPRJ).

Perform all essential dynamics analysis (WEDALL).

Upon calling WEDALL, WHAT IF will ask if the user wants a full automatic mode. If the answer is no, WEDTRA, WEDEIG and WEDPRJ will be called subsequently by WHAT IF just as if they had been called by the user. If the answer is yes, all above analyses will be performed automatically by WHAT IF. The user will only be prompted for a couple of things beforehand and then WEDTRA, WEDEIG and WEDPRJ will be runned subsequently, and no questions will be asked in between. After finishing, WHAT IF will automatically call ANWTRA, ANWEIG and ANWPRJ and present the results of the analysis.