[gmx-users] Re: Folding rate

Sat Dec 31 03:36:48 CET 2011

Yeah sure. There are several methods to trick your peptide to fold, but often you loose the real kinetics by using them. I think a 230 residues protein is too big to study folding kinetics through MD (because of the folding kinetics, not the size of the system). With topology based potenitials (Go-like models) you surely can do it, but take into account the the core asumption there is that the energy landscape of your peptide is perfectly funneled to the native state, which is a very good approximation for small protein (like a 100 residues) but not so nice for bigger proteins. In fact, even small proteins have intermediate states which makes the energy landscape somehow rugged (the engrailed homeodomain, the trp repressor, etc). Besides that, it is not a trivial task to go from the reduced representation to real kinetic constants. Maybe if you are interested in comparison rather than absolute values you can be lucky with the Go-modeling. If that is the case maybe you should try the SMOG potential.... it is very fast.

regards
----Mensaje original---- De: bharat.85.monu at gmail.com Fecha: 30-dic-2011 22:45 Para: "Discussion list for GROMACS users"<gmx-users at gromacs.org> Asunto: Re: [gmx-users] Re: Folding rate  The protein that I am dealing with is a 230 amino acid protein. I have come across some methods that used reduced space model of protein such as CABS for locating the protein folding pathway. An another paper describes about using Go model together with Rigid body dynamics for finding protein folding pathway.  
On Sat, Dec 31, 2011 at 10:23 AM, felmerino at uchile.cl <felmerino at uchile.cl> wrote:

I small thing to consider with that particular paper is that DE Shaw has a special machine (Anton) to do those calculations, so in principle it is not possible to reproduce them (in a reasonable amount of time) on a regular (super)computer. I think your best shot, if your protein is small enough, is to use accelerated MD mixed with some good old kramer's theory. See for example J. Chem. Theory Comput., 2011, 7 (3), pp 575&ndash;581.

In any case it seems to me like too much of an effort, in the end here you really rely in the accuracy of the forcefield.

Regards

----Mensaje original---- De: jmdamas at itqb.unl.pt Fecha: 30-dic-2011 21:40 Para: "Discussion list for GROMACS users"<gmx-users at gromacs.org> Asunto: Re: [gmx-users] Re: Folding rate

  As it was pointed out, the literature is vast on this subject.

Moreover, calculating folding rates from simulations is not a trivial subject, and it relies on many assumptions (e.g. what is considered "folded", that the sampling obtained is enough). Even for small peptides, "enough sampling" may mean several hundreds of microsseconds, something not accessible to everyone.

For a very recent article on the subject, check out:

Lindorff-Larsen, K., Piana, S., Dror, R.O., Shaw, D.E. (2011) How Fast-Folding Proteins Fold, Science 334:517-520.
http://dx.doi.org/10.1126/science.1208351

Regards,
Jo&atilde;o

On Sat, Dec 31, 2011 at 12:19 AM, KS Rotondi <ksr at chemistry.umass.edu> wrote:

As Justin pointed out, there is a vast literature on this topic, you need to ask yourself what you seek, and look at many review articles to find some reasonable starting points for you own needs and designs. Beyond that, it's a lot of hard work...

On Dec 30, 2011, at 7:04 PM, bharat gupta wrote:

Thanks for your advice... Could you please refer me some papers regarding this ....
On Sat, Dec 31, 2011 at 8:17 AM, KS Rotondi <ksr at chemistry.umass.edu> wrote:
No, there is no way to use such data to determine the folding rate of the intact protein. If you used a fragment approach you could potentially (read lots of papers on REMD) isolate nucleation sites, but minus the tertiary interaction scheme you could not tell a compelling story. Now, if you want to find nucleation sites and see if there are spatially proximal sites and simulate them together... You might begin to tell a story.  Ken

  On Dec 30, 2011, at 6:09 PM, Justin A. Lemkul wrote: 
  bharat gupta wrote:
Thanks for your reply. I want to whether does it make any sense or is it possible to simulate fragments of proteins and find their folding rate and then correlate it to folding rate of whole protein ??
 Simulating arbitrary parts of a protein may or may not produce any relevant information, likely the latter.  Independently folding domains might be simulated in isolation, but if there is a chance that the peptide sequences have any effect on neighboring residues or even more distal sites, you'll never produce anything useful.  -Justin 
On Sat, Dec 31, 2011 at 8:00 AM, Justin A. Lemkul <jalemkul at vt.edu <mailto:jalemkul at vt.edu>> wrote:   bharat gupta wrote:       Hi,       I want to know whether it's possible to calculate the folding       rate of 20 residue peptide folding into a beta-hairpin using       gromacs ??   Anything is possible ;)  But seriously, there is existing literature   on such topics, I suspect you can find methodology that will suit   your needs.   -Justin   --     ==============================__==========   Justin A. Lemkul   Ph.D. Candidate   ICTAS Doctoral Scholar   MILES-IGERT Trainee   Department of Biochemistry   Virginia Tech   Blacksburg, VA   jalemkul[at]vt.edu <http://vt.edu> | (540) 231-9080   http://www.bevanlab.biochem.__vt.edu/Pages/Personal/justin   <http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin>   ==============================__==========   --     gmx-users mailing list    gmx-users at gromacs.org   <mailto:gmx-users at gromacs.org>   http://lists.gromacs.org/__mailman/listinfo/gmx-users   <http://lists.gromacs.org/mailman/listinfo/gmx-users>   Please search the archive at   http://www.gromacs.org/__Support/Mailing_Lists/Search   <http://www.gromacs.org/Support/Mailing_Lists/Search> before posting!   Please don't post (un)subscribe requests to the list. Use the www   interface or send it to gmx-users-request at gromacs.org   <mailto:gmx-users-request at gromacs.org>.   Can't post? Read http://www.gromacs.org/__Support/Mailing_Lists   <http://www.gromacs.org/Support/Mailing_Lists> --  Bharat Ph.D. Candidate Room No. : 7202A, 2nd Floor Biomolecular Engineering Laboratory Division of Chemical Engineering and Polymer Science Pusan National University Busan -609735 South Korea Lab phone no. - +82-51-510-3680, +82-51-583-8343 Mobile no. - 010-5818-3680 E-mail : monu46010 at yahoo.com <mailto:monu46010 at yahoo.com>
 --  ========================================  Justin A. Lemkul Ph.D. Candidate ICTAS Doctoral Scholar MILES-IGERT Trainee Department of Biochemistry Virginia Tech Blacksburg, VA jalemkul[at]vt.edu | (540) 231-9080 http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin  ======================================== --  gmx-users mailing list    gmx-users at gromacs.org http://lists.gromacs.org/mailman/listinfo/gmx-users Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/Search before posting! Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-request at gromacs.org. Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
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--  BharatPh.D. CandidateRoom No. : 7202A, 2nd FloorBiomolecular Engineering LaboratoryDivision of Chemical Engineering and Polymer SciencePusan National University Busan -609735 South KoreaLab phone no. - +82-51-510-3680, +82-51-583-8343
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-- BharatPh.D. Candidate Room No. : 7202A, 2nd FloorBiomolecular Engineering LaboratoryDivision of Chemical Engineering and Polymer SciencePusan National UniversityBusan -609735South KoreaLab phone no. - +82-51-510-3680, +82-51-583-8343
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