From: Tristan Croll (tristan.croll_at_qut.edu.au)
Date: Mon Jul 14 2014 - 00:40:11 CDT
If you’re going to try an accelerated MD approach like this I would recommend at the very least applying cispeptide restraints to all mobile residues (with perhaps the exception of X-Pro).
From: owner-namd-l_at_ks.uiuc.edu [mailto:owner-namd-l_at_ks.uiuc.edu] On Behalf Of James Starlight
Sent: Monday, 14 July 2014 5:05 AM
To: Namd Mailing List
Subject: Re: namd-l: accelerated MD as the engine for loop refirement
oh sorry it was quite difficulte to send message from the mobile phone :-) so I'd to specify my question.
1 )Regardless of the enhansed sampling method I wounder if the simulation of membrane protein in principle will be possible placing the protein within the water box (not into the membrane) and with the application of the restraints on its all atoms (to prevent its unfolding due to its contact with the water not with the membrane) apart from the loops which should be refined (which are in both cases will be accesible to water)?
2) Had someone been experienced with the rosetta package for loop modelling in case of membrane proteins? On what general ideas such refirement is based?
James
2014-07-12 18:28 GMT+04:00 James Starlight <jmsstarlight_at_gmail.com<mailto:jmsstarlight_at_gmail.com>>:
Thanks alot!
Some additional question:
Assuming that I need to refine loops quickly of my membrane receptor what should be expected if I 1) place the whole protein into the water box (no membrane) 2) apply position restraints onto the all parts of this protein which in fact must be embedded into the membrane to artifacts of its contact with water (not membrane) in my model 3) run some enhansing sampling engine to sample loops only in water box keeping all other parts frozen. Could some artifacts in loops be arrise due to such coarse-graining of the environment?
James
2014-07-11 2:59 GMT+04:00 Gianluca Interlandi <gianluca_at_u.washington.edu<mailto:gianluca_at_u.washington.edu>>:
Why not just running accelerated MD and explicit solvent? That might already confer an idea of the flexibility of the loops. Another alternative is to use metadynamics (implemented as COLVARS in NAMD or through the plumed plugin) and explicit water. Metadynamics should be more efficient than accelerated MD once you have identified the correct collect variables.
You can also try out implicit solvent on its own or couple it with REM. But I would always test those things independently before combining them.
Gianluca
On Thu, 10 Jul 2014, Kenno Vanommeslaeghe wrote:
It all depends. These loops often require very long timescales to get descent sampling, such that the sampling error when using explicit solvent might be greater than the error in the implicit solvent energetics. Though I have no idea whether there's any specific crosstalk between Accelerated MD and implicit solvent (my guess would be "no" but that's just a guess).
On 07/09/2014 04:08 PM, Gianluca Interlandi wrote:
Accelerated MD + implicit solvent. In my opinion, that might cause too
many distortions. It's a good start to get an idea of the accessible phase
space but whether that will really tell you the most likely conformation
nobody can say for sure. I would use regular MD in explicit solvent
coupled with something like REM. But that is just my 2c.
A good start would be to simply run two MD simulations in explicit water
at 300 and/or 310 K (50 - 100 ns) and see what those loops do.
Gianluca
On Wed, 9 Jul 2014, James Starlight wrote:
Dear NAMD users!
I wounder whether the accelerated molecular dynamics might be good
solution for the
loop refirement of models made by means of hoology modeling with the
teplated which
has the low sequence identify in loop region? For instance I've just
built some
models of membrane receptors agains receptor with known structures and
would like to
refine loops by some enhansed sampling engine to sample all possible
conformation and
found most propable during short simulation. Does the acceleraed md good
sollution
for such task assuming simulation with implicit solvent with restrained
all atoms of
the helix regions of the refined protein but not loops flexible region?
What
alternatives should I explored also?
TFH,
James
-----------------------------------------------------
Gianluca Interlandi, PhD gianluca_at_u.washington.edu<mailto:gianluca_at_u.washington.edu>
+1 (206) 685 4435<tel:%2B1%20%28206%29%20685%204435>
http://artemide.bioeng.washington.edu/
Research Assistant Professor at the Department of Bioengineering
at the University of Washington, Seattle WA U.S.A.
-----------------------------------------------------
-----------------------------------------------------
Gianluca Interlandi, PhD gianluca_at_u.washington.edu<mailto:gianluca_at_u.washington.edu>
+1 (206) 685 4435<tel:%2B1%20%28206%29%20685%204435>
http://artemide.bioeng.washington.edu/
Research Assistant Professor at the Department of Bioengineering
at the University of Washington, Seattle WA U.S.A.
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