On 07.01.2009, at 22:54, Jacob Keller wrote:
These cases, however, presuppose that one knows which type of case
one is dealing with. This could be done by guesswork and trial-and-
error, but does anybody know of an approach (e.g., a program) to
define the most reasonable way to think about a given
conformational change? Variable-size sliding-window least-squares
superpositions with comparisons of local versus global rmsd's come
to mind, but I do not know whether this has been implemented
anywhere, and would not know readily how to set the parameters
thereof either.
As you say quite correctly, what you want to optimize is the "way to
think about" a conformational change. Since this is a mental rather
than a physical criterion, I wouldn't expect any mathematical
approach to give an answer. I think you will have to choose your
criteria based on the interpretation you want to make, and only then
invoke mathematics to do the computation.
For any purpose other than visualization, and in particular for any
quantitative analysis, I strongly recommend to look only at changes
in scalar functions of atomic positions, which do not depend on the
orientation of the whole protein. The probably most widely used
analysis of this kind is a difference-distance map, but many others
can be defined. For example, flexibility in a protein can be
quantified by defining a local deformation energy: imagine a spring
between each pair of atoms (up to a certain distance), and calculate
the energy change in the spring network when moving from one
conformation to another. This deformation energy is high in flexible
regions and low in nearly rigid domains. This approach is described in
K. Hinsen et al., "Analysis of domain motions in large proteins",
Proteins. 34 (1999): 369-382
http://dirac.cnrs-orleans.fr/plone/publications/preprints/all-
preprints/domain_motions.pdf/view
and implemented in the DomainFinder program:
http://dirac.cnrs-orleans.fr/DomainFinder/
as a preliminary step before domain analysis. After all, there is no
point in looking for domains in flexible regions of a protein.
In a protein with clearly defined domains, you can also look at their
relative motion (translation, rotation) without any reference to
absolute orientations. In fact, I suppose that most conformational
changes in proteins can be described in a useful way without any
initial superposition.
Konrad.
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Konrad Hinsen
Centre de Biophysique Moléculaire, CNRS Orléans
Synchrotron Soleil - Division Expériences
Saint Aubin - BP 48
91192 Gif sur Yvette Cedex, France
Tel. +33-1 69 35 97 15
E-Mail: [email protected]
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