[gmx-users] Essential dynamics - concepts

[Kavyashree M]

Dear Gromacs users,

 I am new to essential dynamics, I have gone through
some fundamentals in PCS, the mailing list related to ED
and few publications by -
Amadei (Proteins, 17, 412-425, 1993),
a. Amadei (journal of biomolecular structure and dynamics, 13, 615, 1996)
b. Berk Hess (Physical reviews E, 62, 8428-8448, 2000)
c. Berk Hess (Physical reviews E, 63, 031910, 2002)
d. Caterina (Biophysical chemistry, 92, 183-199, 2001)

I have made a short note of what I understand. Please correct.
the mistakes.
1. ED is principally used to study the anharmonic motions, ie those
   which are not equilibrated unlike equlibrated motions like bond
   vibrations, bending etc.. (Equilibrated in the time scale of study)

2. So one has to run a simulation long enough so that it is more than
   or equal to the time scale required for the specific motion (for eg.
   closing of loop takes place in few ps, one has to run MD for atleast
   a ns to investigate it)

3. After MD for long enough time, when covariance matrix would indicate
   whether two atoms move in same direction, or opposite over the time
   of simulation based on positive or negative value. Extracting Eigenvalues
   and Eigenvectors from the matix gives the directions in which the highly
   correlated motions occur.

4. Analysing all the data values projected over the first few eigen vectors
    is the priciple component analysis.

5. if this experiment is done on same structure more than once (say 3), and
the
    first few priciple components of all 3 simulations coincide, then it
could be
    the most possible direction of motion in the protein otherwise the
patern
    of PC's is most likely due to random motion.

My questions -
1. While chosing the period for covariance analysis, what is the criteria?
in the
    paper b, author mention that a certain peroid was chosen because the
peptide
    free enegry minimum. Not clear about this, because when the protein
resides in
    an energy minimum how can there be transition to another configuration
(eg a loop
    movement) without crossing the barrier. should we not consider the time
which
    spans a native conformation to say an active conformation during the
simulation?

2. If we have done a long enough simulation of say 100ns for 4 proteins with
similar
   structure but with sequence id of 40-60% (different chain lengths
230-260aa), Can
   we do a covar analysis of these 4 simulations?

3. How much should be the socine content to tell that it is not a random
diffusion?

4. Is ED analysis itself is not enough to establish a important movement in
the
    protein.. further ED sampling is required to prove it?

5. Concept doubt - When all the structures at least square fitted before
building a
    covariance matrix, where is the random diffusion comming into picture? I
am
    sorry I was not clear about this consept qualitatively.

6. I am working on a enzyme whcih upon binding to substrate shows a marginal
    deviation from the native unbound structure. I have onlt the unbound
form, but
     the two forms are available in other organisms whose structures are
very similar
     to the one I am working. So would you think doing the ED on this
protein is
     logical?

I was not recieving replies form the forum for my rescent queries (which I
had to obtain
from my senior, SO kindly check if there is any problem)

I AM EXTREMELY SORRY FOR VERY BIG MAIL.!!

Thanking you
With Regards
M. Kavyashree
-------------- next part --------------
An HTML attachment was scrubbed...
URL: <http://maillist.sys.kth.se/pipermail/gromacs.org_gmx-users/attachments/20110604/646d1471/attachment.html>