AMBER Archive (2008)

Subject: RE: AMBER: change in secondary structure during MD

From: Ibrahim Moustafa (I.moustafa_at_psu.edu)
Date: Thu Feb 28 2008 - 16:12:49 CST

Thanks for Yong and Carlos for their comments.

 First, pardon me for not giving the details of the MD run in the first
instance.
The MD was run using AMBER9-ff99. The protein (53 kDa, 461 aa) was solvated
in Octa unit cell and neutralized with 6 Na+; this sums to a total number of
82,000 atoms. (This would exclude any comments assuming the use of GB
model).

 The system was prepared by first minimization (alternating with Belly
dynamics and NPT on the system being minimized), heating to 300 K at steps
of 50 degrees (total 150 ps) with coupling "tautp=0.05", equilibrated
further at 300 K for another 200 ps and using the same coupling)...these
done using NVT model. Then the run was pursued using NPT for total run time
of 5 ns (the intention is to continue the run even longer after analyzing
the short 5 ns run (well, relatively speaking it is short by current
computing standards).
 
 Throughout the whole run, the behaviors of TEMP, ENERGY, and DENISTY were
excellent...no sign for any unusual behavior during the run.

   Then the preliminary analysis showed the sec. structure changes as posted
in my previous e-mail.

  Looking forward to hear more from your experiences.

  Regards,
  Ibrahim

-----Original Message-----
From: owner-amber_at_scripps.edu [mailto:owner-amber_at_scripps.edu] On Behalf Of
Yong Duan
Sent: Wednesday, February 27, 2008 9:13 PM
To: amber_at_scripps.edu
Subject: RE: AMBER: change in secondary structure during MD

All sound pretty reasonable to me :)

Seriously, 5ns is not too short to see changes like that if they are not
stable to begin with. Surface loops can change, exposed strands can also
become loops, short helices are not very stable.

The secondary structure stability (or lack of) in AMBER is not an inherent
feature of AMBER, but more closely related to force field you are using. If
you can let us know which force field you used and how you performed the
simulations, we probably can "guess" what you see could be artifact of
simulation. Treat our comments as 0th order approximation, though. You still
need to investigate.

yong

-----Original Message-----
From: owner-amber_at_scripps.edu [mailto:owner-amber_at_scripps.edu] On Behalf Of
Ibrahim Moustafa
Sent: Wednesday, February 27, 2008 5:45 PM
To: amber_at_scripps.edu
Subject: AMBER: change in secondary structure during MD

Dear amber users,

  I did a 5ns MD run on a protein using AMBER9. The analysis of the run
showed that, overall, the structure averaged over the last 500 frames is
pretty similar to the crystal structure after the run, apart from meaningful
dynamics at some parts. However, while investigating the structure in Pymol,
I noticed that there is a change in some secondary structure elements. More
specific: a couple of B-strands changed to loops, two short parts of long
loops turned to B-strands and finally, a short helix turned into a loop. I
know I do need to investigate this further by calculating the secondary
structure following DSSP. But, visually I can feel the changes mentioned
above.

 I understand that, in principle, a change in secondary structure could
happen during MD, as a non-folded structure can be folded during simulation.
But, I want to be sure that what I see is not an artifact of the simulation.
I remember I came across some comment about the sensitivity of AMBER to
B-strands stability compared to helices. Of course, this comment could be
true for the previous versions of the program (I'd love to hear the
developers' comments on that) which might be not the case for the current
version.

 I'd appreciate if people with more experience could give me their opinions,
and point me to publications where secondary structure change is reported.

  Thanks in advance of your help and your valuable comments.

  Regards,
  Ibrahim

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