[gmx-users] Simulation of slow folding proteins

Tsjerk Wassenaar tsjerkw at gmail.com
Tue Mar 22 06:27:32 CET 2011

Hi Bharat,

In addition to the good comments from Chris, mind that to understand
the molecular nature of experimental observations like yours requires
quite a bit of statistics. With just two cases - wild type and
insertion - there is too much uncertainty to claim that possible
differences you observe between the two in a limited (or even
infinite) stretch of time are linked to the difference in the test
tube. Part of them might, but the answer could well be hid in some
unexpected property that is overwhelmed by a seemingly obvious
difference. You would need to have experimental and simulation data on
a whole series of mutants to be able to regress one to the other, and
hope that the differences manisfest themselves in properties that can
be assessed in simulations on the time scales accessible.



On Tue, Mar 22, 2011 at 2:02 AM,  <chris.neale at utoronto.ca> wrote:
> Dear Bharat:
> I hope that this doesn't impede others giving you advice about how to go
> about doing what you want to do, but here's my two cents for what it's
> worth:
> My suggestion is to forget about trying to do that. 3-ns simulations are not
> going to give you equilibrium populations of conformational basins (and
> neither would 3-us simulations, I suspect). Not every question is amenable
> to MD on the currently available timescales.
> If you really want to try to do it, I would find out what conformations lead
> to flourescence and see if you get more drift away from those conformations
> in some models with longer loops. But again, I think it's probably going to
> be a waste of time.
> Chris.
> -- original message --
> Hi,
> I simulated a protein (GFP) with one of its loop replaced with a longer loop
> . After simulating for some 5 to 10 models with different loop sequences , I
> decided to carry out wet-lab experiments for one model on the basis of
> simulation result. The analysis of simulation was done in the following way
> :-
> 1) Comparison of RMSD values of backbone - for both GFP wild type and loop
> replaced (mutated GFP)
> 2) Comparison of RMSF of the residues common to both the proteins.
> 3) Visual Inspection of entry of water into GFP.
> The simulation was carried out for 3ns for both the proteins.
> After that I did the wet-lab experiment for the modeled structure and I
> found the fluorescence to be 50% of the wild type.
> Now I want to investigate the reason for this reduction in fluorescence
> ??... How can this be quantified using MD.
> --
> 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
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Tsjerk A. Wassenaar, Ph.D.

post-doctoral researcher
Molecular Dynamics Group
* Groningen Institute for Biomolecular Research and Biotechnology
* Zernike Institute for Advanced Materials
University of Groningen
The Netherlands

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