DynDom is a program to determine domains, hinge axes and hinge bending residues in proteins where two conformations are available.

This website provides access to the DynDom program and its associated databases. There are five databases: the user-created database that accumulates successful DynDom runs submitted by users, the non-redundant database that arose from an exhaustive study of X-ray structures in the PDB, a database of ligand-induced domain movements in enzymes, a database that classifies domain movements based on Dynamic Contact Graphs, and a database that classifies movements based on the effect on the domain interface.

When to use DynDom

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 assess this, but the results could be misleading if this is not the case. DynDom allows you to visualize the domain motion in terms of the rotation of one domain relative to another. Here we see the motion of the red domain relative to the blue domain that occurs upon substrate binding in citrate synthase. The arrow indicates the hinge axis and green those regions where the hinge bending takes place.

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Determination of Dynamic Domains

The program initially determines the "dynamic domains." First, a whole protein best fit of the two conformations is made. Then, rotation vectors of short main-chain segments are determined. A clustering algorithm is then used to identify clusters of rotation vectors. Residues from segments in an individual cluster form a possible dynamic domain.

Determination of 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."

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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. If the clusters are treated as 3-dimensional normal distributions then bending residues are those that lie outside the ellipsoids of constant probability density that correspond to a significance value P of 0.2.

Closure and Twist Motion

Axes can be classified into two extreme 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.

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