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This is version 2.0.5 of DomainFinder, an interactive program for the determination and characterization of dynamical domains in proteins. This program is copyrighted but free to use for anyone under the CeCILL-C License, see the file LICENSE for details.

DomainFinder should work with all major variants of Unix. There is no system-specific code in DomainFinder itself, so porting DomainFinder to non-Unix systems should be easy. However, I cannot provide any support for this.

If you have any questions about DomainFinder that are not answered on the Web page mentioned above, please contact the author.

Konrad Hinsen Centre de Biophysique Moleculaire (CNRS) Orléans, France

AND

Synchrotron Soleil Division Expériences Saint Aubin - BP 48 91192 Gif sur Yvette Cedex, France

E-Mail: konrad.hinsen@cnrs.fr

Installation

DomainFinder requires the Python interpreter (version 2.3 or higher) with the Tk interface installed, and the Molecular Modeling Toolkit (MMTK), version 2.4 or higher. Make sure that these components work properly before installing DomainFinder. The MMTK example scripts should work, as well as the Tkinter Demo programs from the Python distribution.

Then type

python setup.py install

On most systems this will require root permissions, as by default the files will be installed in the same directory as the Python interpreter. Other directories can be specified, type

python setup.py --help install

for explanations. Once installation is finished, type

DomainFinder

to run the program.

When dealing with very large proteins, it can be of interest to perform the normal mode calculation on a faster machine or on a machine with more memory than the workstation used for visualization. Sometimes computers dedicated to number crunching applications do not provide a graphical user interface, and then the DomainFinder program cannot be run.

A seperate program called DomainFinderModes is therefore provided to calculate the normal modes and save them to a file, which can then be transferred to the workstation and analyzed with DomainFinder. To execute this program, type

DomainFinderModes pdb-file mode-file modes-saved modes-calculated

The first argument is the PDB file from which the protein conformation is read. The second argument is the name of the mode file to be created. The third argument indicates how many modes should be kept in the file, and the fourth argument specifies the number of modes to be calculated. See the DomainFinder manual for a discussion of the meaning of these parameters.

Documentation

The directory Doc contains the DomainFinder manual in two formats: HTML and SGML/Linuxdoc.

Visualization examples

While the graphics displays in DomainFinder are sufficient for interactive analysis, it is often desirable to produce high-quality images for publications and presentations. These can be produced by saving modes and/or domains (in MMTK format) and using appropriate Python scripts (using MMTK) for visualization.

Two example scripts can be found in the directory Visualization. The script vector_field.py visualizes atomic displacements in a given normal mode by arrows placed on a grid. The script visualization.py shows the domains by colors and their movements in a given mode by a scre-motion axis and an arrow. Both scripts require the molecule viewer VMD, which is available from http://www.ks.uiuc.edu/Research/vmd/. Using the rendering functions of VMD plus ray-tracing programs, very high quality pictures can be produced.

Domain motion amplitude calculations

When studying a conformational transition, it is often of interest to know by how much a given domain moves during that transition. This information is given by the script DomainMotionAmplitudes.

The script is used as follows (all on one command line):

DomainMotionAmplitudes struct1.pdb struct2.pdb
alignment_region domain_1 domain_2 ...

Any number of domain specifications can be given, the calculation is performed for each domain. The alignment region defines the part of the protein that is superposed optimally prior to the other calculations. The alignment region can be the whole protein, or a part of it that serves as a reference.

The alignment region and the domains are specified by chain and residue numbers. The simplest specification is a residue number (e.g. 5) or a range of residue numbers (e.g. 2-8). By default these refer to chain number 1. A chain number can be given as a prefix, e.g. 2:4-45 for residues 4 to 45 (inclusive) in chain 2. To specify a domain or an alignment region that consists of several chain segments, join the segment specifications by a plus sign (+). Note that no specification may contain spaces anywhere, because space are used to seperate specifications.

An example of a more complex domain specification is

1:11-50+1:81-99+2:32-67

This stands for residues 11 to 50 and 81 to 99 of chain 1 and residues 32 to 67 of chain 2.

Analyzing domain motions by normal mode decomposition

Another useful analysis is the decomposition of the rigid-body motions of a given domain into the normal modes of a protein. Such an analysis reveals how well-defined a domain is and at what energetic cost its displacements are possible. The analysis is performed by the script RigidBodyMotionsByMode, which is used as follows:

RigidBodyMotionsByMode mode_file rb1 rb2 ...

The first argument is the name of a file containing the normal modes of the protein, such as produced by DomainFinder or by the script DomainFinderModes. The remaining arguments are the specifications of any number of rigid-body groups. A rigid-body group can be a single rigid body, i.e. a domain, which is specified exactly as for the script DomainMotionAmplitudes (see preceding section). However, it can also be a group of several rigid bodies, whose definitions are separated by commas (again, be careful not to insert any spaces).

The output of the script is a file called rigid_body_motions_by_mode.plot. It contains for each rigid-body group a list of numbers, the lists being separated by a blank line. Each list contains a number for each mode. This number represents the sum of the projections of this and all prior modes onto the direction vector corresponding to the rigid-body motion under study. If all modes of the protein are used in the analysis (i.e. if the mode file contains a full set of normal modes), the last number must be 1. The cumulative projection can be interpreted as the percentage of the rigid-body motion that can be described by a given number of modes. For a well-defined domain that participates in low-energy collective motions, the cumulative projection rises quickly from zero to one. For a region that undergoes significant internal deformation (i.e. which is not really rigid) or which moves only in association with high-energy deformations around it, the increase from zero to one happens slowly.

Transition path calculations

The script TransitionPath calculates a transition path between two conformations of a protein. This transition path is constructed on the basis of a flexibility analysis of the protein using the same elastic network model that DomainFinder uses. The initial conformation is deformed towards the final conformation taking into account the flexibility. The resulting transition path is thus compatible with the constraints imposed by the protein structure. However, it would be inappropriate to call it the transition path. Other paths are possible, and very probably several paths occur in real-life coformational changes.

The script is used as follows:

TransitionPath struct1.pdb struct2.pdb trajectory.nc nsteps

where struct1.pdb represents the initial configuration, struct2.pdb the final configuration. The resulting path has nsteps steps and is stored in the file trajectory.nc (an MMTK-format trajectory).