Molecular dynamics

Gerard Pujadas g.pujadas at ibcp.fr
Mon Jun 11 04:23:25 EST 2001

	Dear Bionet community,

	First of all, sorry if you have received the following message by a
different way:

	I would like to analyze the dynamics of water movements in the
active site of an enzyme upon substrate binding. I think that the best
theoretical approach to do that is molecular dynamics (MD), although I am
not sure (I have never used MD soft and therefore, I don't know which are
their capabilities and/or limitations). Therefore, I would appreciate very
much your answers, comments or suggestions.

The scientific problem is the following:

We have two structures for the same protein, one corresponds to the free
enzyme and the other corresponds to a complex of this enzyme with a
substrate analog. Both structures have good resolution (1.85 and 1.74 Å)
and therefore, the waters  around the active site are well seen. Our aim is
to study how the crystallographic waters in the free enzyme have moved upon
substrate binding. In other words, we would like to follow which has been
the "trajectory" of each active site crystallographic water upon ligand
binding in order to identify which coordinates correspond to the same water
but before and after the displacement. Therefore, I think that we would
need to have the PDB files corresponding to the different "snapshots" when
going from the free-enzyme to the complexed structure.

Therefore, my questions are:

* Is MD applicable to my problem? If not, is there any other valid
theoretical approach?

* What programm do you suggest me to carry out this study? It is also
essential that this program provides me also with the "PDB files" for the
different snapshots when going from the free to the complexed state (these
"PDB files" would allow me further analysis with the GRID soft).

* As I have previously said, this is my first experience with MD software.
Therefore, I am not very sure about how to build the starting PDB file.
Obviously,the free structure has no coordinates for the substrate analog.
In fact, in the start, it is expected to come from the outside of the
enzyme (difusion?). Therefore, I suppose that the starting PDB file must be
built with the enzyme+water from the free structure plus the substrate
analog outside the enzyme. The problem here is where in the outside of the
enzyme is the correct place to put the substrate (how far from the active
site or the enzyme and in which position). I think that it is also
important to think on the orientation of the ligand. Are there any rules
for that?.

I would appreciate very much if you could point me to some bibliography
that deal with studies similars to the one that I would like to make.

Thanks in advances for your time and help. Please, do not hesitate to
contact me if you need further information.

Best regards !!!


Dr. Gerard Pujadas
Laboratory of Bio-Cristallography		e-mail: g.pujadas at ibcp.fr
Institut de Biologie et Chimie des Protéines	phone: +33 (0)
Unité Mixte de Recherche 5086 du C.N.R.S.	fax: +33 (0)
7, passage du Vercors - 69367
LYON cedex 07 - FRANCE

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