From: Gianluca Interlandi (gianluca_at_u.washington.edu)
Date: Tue Jul 15 2014 - 02:05:30 CDT
I think that the question that needs to be asked here is: What exactly do
you plan to do with the structure after you have refined the loops? I
guess that might influence what method you need to use for this task.
Gianluca
On Mon, 14 Jul 2014, Ramin Ekhteiari wrote:
> I had a experience like your project, I preformed Rosetta de-novo loop predation by using 3
> and 9 residues fragment generated by Robetta server, I remodelled and refined the loops of
> 10,000 models.
>
> Cheers,
> Ramin.
>
>
> On Tuesday, July 15, 2014 2:20 AM, Tristan Croll <tristan.croll_at_qut.edu.au> wrote:
>
>
> It would be best if I deferred to the experts on your more detailed questions. The only
> point I wanted to make is that with any method that adds substantial amounts of energy to
> your system (whether it be aMD or REMD) you?re increasing the risk of inducing
> non-physiological conformations. The most obvious of these is the flipping of backbone
> peptide bonds into the cis conformation.
>
> From: James Starlight [mailto:jmsstarlight_at_gmail.com]
> Sent: Monday, 14 July 2014 8:17 PM
> To: Tristan Croll; Namd Mailing List; Jeff Wereszczynski
> Subject: Re: namd-l: accelerated MD as the engine for loop refirement
>
> Hi Tristan,
>
> most people suggest me to use REMD instead of aMD for loop refirement because AMD might
> seriously alter thermodynamics of the system (during rewealling for instance). This will
> result in the non-physical conformations of the refined loops because of the non-bolzman
> distribution pattern obtained after AMD. What do you think about it? Also It'be very
> interested to know Jeff's opinions about such topic because of its great experiuence in
> this method.
>
>
> James
>
> 2014-07-14 9:40 GMT+04:00 Tristan Croll <tristan.croll_at_qut.edu.au>:
> 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>:
> 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>:
>
> 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
> +1 (206) 685 4435
> 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
> +1 (206) 685 4435
> 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
+1 (206) 685 4435
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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