[gmx-users] Regarding Pulling simulation:To study the base flipping of the thymine

[Christopher Neale]

What you are talking about with conducting only 2 end-state simulations sounds like "free energy perturbation" and
it relies on conformational overlap of the two endstates. I don't think that it is going to give correct free energies
here. The reason to do umbrella sampling (US) is to ensure that there is conformational overlap. In any event, I would
be very cautious about using a two-state computation like that, even if you don't care about the shape of the
curves. As a final note, the shape of the US curves doesn't necessarily give you useful information either. The
shape of the curve depends on the pathway and thus the order parameter that you chose. It may or may not
be relevant to the most likely path followed in unrestrained simualtions.

Chris.

 -- original message --

Ill give this a shot.  I guess it depends on your entire system (ie protein +DNA or just DNA) and what it is you waant to observe.

and example of why answereing becomes complex.  if A) I want to just look at say the total delta G,S or H.  I would only need to EQ several starting structures of the Thymine in conformation A, then several in conformation B. Then allow each to just run for a reasonable amount of time, in an NVT system. Then, you can just use the differences from the two to calculate the total energy change, but get no pretty curves, just simply a value.  This is relativly quick as it is essentially just long EQs.  I have done this, and it it fits biochem data from liturature.  But B) However, say you want the curves, or to compare positional or distance or other things (ionization, solvation), Then you have to take into account what you want to apply force on, ie a protein, the DNA as a whole or at varied positions along the bases, etc...and then follow the online tutorial for pull simulations.  If you are doing this and it is say just DNA, you then have to do dozens of runs, pulling along e
 ach base and holding the other fixed within reason,(like the complement, then the two on either direction or more...) most likely at several adjascent positions...to get a reflection of the real system.

Hope that helps in some way.  

Stephan Watkins

-------- Original-Nachricht --------
> Datum: Tue, 18 Sep 2012 02:52:46 +0000
> Von: Christopher Neale <chris.neale at mail.utoronto.ca>
> An: "gmx-users at gromacs.org" <gmx-users at gromacs.org>
> Betreff: [gmx-users] Regarding Pulling simulation:To study the base flipping of the thymine

> You can do this with the pull code. To do so, you need to define some sort
> of order parameter for which you have the base flipped in at one extreme
> and the base flipped out at the opposite extreme. There are lots of ways to
> do this and, unfortunately, there is no way to know what the best order
> parameter is without first evaluating it. Therefore, I suggest that you start
> with something simple like the distance between the NH of thymine and the
> NH of the paired guanine (assuming that you really have a TG pair). To pick
> the atom pair for the distance restraint, you can ideally look at a
> structure of equilibrium close association and find a pair of heavy atoms that are
> close.
> 
> Chris.
> 
>  -- original message --
> 
> I am studying a system which consists of DNA duplex 20 base pairs.
> Actually
> I am interested in studying the base flipping of  the thymine.
> I have the crystal structure of extrahelical DNA  in which thymine is out
> side the helical structure. I want use pulling simulations to bring this
> base from extrahelical to Intrahelical  conformation, is there any way to
> do it in GROMACS pull code. Please see the figure below (link) for
> description.
> http://researchweb.iiit.ac.in/~kartheek.p/extrintra.png
> 
> -- 
> Thanks and Regards,
> kartheek,
> -- 
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