DYNDOM (CCP4: Supported Program)
NAMEdyndom - determine dynamic domains when two conformations are available
For complete and up-to-date information, see the DynDom Home Page.
DynDom is a program that determines protein domains, hinge axes and amino acid residues involved in the hinge bending. It is fully automated.
You can use DynDom if you have two conformations of the same protein. These may be two X-ray structures, or structures generated using simulation techniques such as molecular dynamics or normal mode analysis.
The application of DynDom provides a view of the conformational change that is easily understood. The conformational change may be quite complicated in detail, but by using DynDom you can visualize it as involving the movement of domains as quasi-rigid bodies. The analysis of a conformational change in terms of domain movements only makes sense if the interdomain deformation is at least comparable to the intradomain deformation. You can use DynDom to access this, but the results could be misleading if this is not the case.
INPUT AND OUTPUT FILES
rasmol foo_rotvecs -script foo_rasscriptTo display the protein to view the domains etc, simply enter the command:
rasmol foo_pdb -script foo_rasscript
windowA sliding window is used to generate backbone segments whose rotation vectors are calculated for the clustering algorithm. The longer the window the better local intrasegment rotations, which may have nothing to do with the domain motion, are eliminated. A shorter window, however, is preferable if one wants to accurately identify those residues involved in the interdomain bending. In any case the length of the window should be short compared to the minimum domain size. The length of the window is specified by the number of residues. The length of the window must be odd as the central residue must be defined. Default=5
domainThis sets the minimum domain size in number of residues. It depends on your feeling on how big a domain should be, to be called a domain. It can be set as small as you like, but it wouldn't be logical to make it smaller than the window length. Default=10% of total number of residues
ratioThis value gives the minimum value for the ratio of interdomain displacement to intradomain displacement for a domain pair. For a precise definition of this value see the DynDom main reference. There is no clear cutoff for this value, but the lower it is for a domain pair, the less sensible it is to analyse their motion in terms of an interdomain motion. The program calculates this value for every prospective domain pair and outputs it to the screen. If you set the minimum to a value much less than 1.0 you may end up analyzing meaningless results. Default=1.0
Description of the Basic Methodology
Determination of Dynamic Domains
The program first determines the "dynamic domains." First, a whole protein best fit of the two conformations is made. Then, rotation vectors of residues or short main-chain segments are determined. A clustering algorithm is then used to identify clusters of rotation vectors. Groups of residues forming these clusters form possible dynamic domains.
Determination Hinge Axes
Groups of residues are only accepted for the analysis of hinge axes if they satisfy a criterion based on the ratio of the interdomain displacement to intradomain displacement with another group of residues with which there exists a physical connection. If this is the case the two groups of residues form dynamic domains and their interdomain motion is meaningful. The axes determined are in fact interdomain screw axes. This is based on the theorem of Chasles which states that the general displacement of a rigid body is a screw motion. The location of the interdomain screw axis tells us something about the kind of motion allowed by the interdomain connections. It is possible for the interdomain screw axis to be located far away from the interdomain connections if they are very flexible. Only if the interdomain screw axis is located near to those residues involved in the interdomain bending (defined below) can we think of the axis as a hinge axis. In such a case we call the axis an, "effective hinge axis" and the residues are said to be acting as "mechanical hinges."
Determination of Residues Involved in Interdomain Bending
If one domain is fixed in space with the other rotating, then one will see a rotational transition in the connecting region between the two domains. One can define the residues involved in the interdomain bending to be those at the interdomain boundaries, as found by the clustering algorithm, plus those neighbouring residues whose rotations are outside the main distribution of the domain to which they belong.
Closure and Twist Motion
Axes can be classified into two extrme types: those parallel to the line joining the centres of mass of a pair of domains, and those perpendicular to this line. The former are called twist axes, the latter, closure axes. Any axis can be decomposed into components parallel or perpendicular to this line and a percentage measure of the degree of closure motion can be defined from the square of the projection on the closure axis.
How DynDom Works
DynDom uses the K-means clustering algorithm to find clusters of rotation vectors. The number of clusters found is specified by the user, but should be set high as DynDom automatically finds the largest number of clusters for which one may reasonably regard the conformational change in terms of domain motions.
DynDom uses the K-means clustering algorithm to find clusters of rotation vectors.
A cluster in rotation space may not correspond to a cluster in real space, but rather a fragmented region. Such a fragmented region one would not normally call a domain. DynDom splits up any clusters that do not correspond to heavy atoms connected through a network of distances of 3.5 angstrom or less, into domains. In order for DynDom to analyse domain pairs in terms of their interdomain movement two criteria must be satisfied. The first concerns the minimum domain size. If a domain comprises fewer residues than the minimum domain size set by the user, then segments from this domain are united with the larger domains they are embedded in. If all the domains from any single cluster are smaller than the minimum domain size, the program stops, unless this the first cluster found (K=2).
For every domain larger than the minimum size, the program checks which are connected directly through the backbone (not through another domain), and calculates the ratio of interdomain displacement to intradomain displacement for every connected pair. If this ratio is less than the user specified minimum (the second criterion) then then this pair are not analysed. The program finds the largest number of clusters for which all connected domain pairs that satisfy both criteria. It is these domain pairs that are analysed in terms of interdomain screw axes, etc. If this is not possible it will analyse any domain pair for interdomain screw axes, etc, provided that the two criteria are satisfied.
EXAMPLESExample script for adenylate kinase can be found in $CEXAM/unix/runnable/