I've had some luck reproducing B-Z coexistence parameters wrt salt
concentration using Joung-Cheatham ion parameters and 99-bsc [
http://pubs.acs.org/doi/abs/10.1021/ct3005968 ]
Free energy difference between the two forms is not the same thing as
kinetics of the interconversion, but its at least an encouraging sign.
The work is 5-years old now...
Josh
On 28 January 2017 at 21:29, Debayan Chakraborty <debayan.ch.gmail.com>
wrote:
> Dear Yogeshwar,
> I think Prof Sponer is absolutely spot on. The
> B-DNA to Z-DNA transformation is one of the slowest transformations in
> biology, and it is really unlikely to ever occur during unbiased MD.
> Several groups have used targeted MD or adaptively biased MD to study this
> transition. Recently, we looked at the B to Z transformation using the
> Discrete path sampling technique, and the pathways that we found looked
> pretty complex, with barriers which are much higher than kT. We used the
> ff99bsc0 force-field with the epsilon-zeta corrections (see Zgarbova et.
> al., JCTC, 14, 2339, 2013). The topography of the free energy landscape
> that we found suggest why you would never see the B-> Z transition on the
> time scale of a typical MD, and B-DNA is the global minimum under
> physiological conditions.
>
> You suggested that you saw the alpha, gamma, epsilon and zeta angles change
> during MD, but again without the chi torsional flips one cannot reach the
> B-DNA structure starting from Z-DNA. Are you sure that the structure that
> you see is not a left-handed form of B-DNA ? What checks have you performed
> (In terms of minor groove width, helicity, etc...) to confirm that the
> structure you see at the end is indeed the canonical form of B-DNA ?
>
>
> Best,
> Debayan Chakraborty
> Postdoctoral research scholar,
> The University of Texas at Austin, USA
>
> On Thu, Jan 26, 2017 at 7:55 AM, Yogeeshwar Ajjugal <
> bo14resch11004.iith.ac.in> wrote:
>
> > Dear all,
> >
> > The formation of B-Z junction is provoked by many conditions including
> the
> > presence of A...A mismatches, as reported by Khan et al in Plos
> > Computational Biology ( DOI :10.1371/journal.pcbi.1004162). I observe
> that
> > in ff99SB forcefield my DNA which has B-Z junction initially remains
> > unchanged till the end of the simulation, whereas in leaprc.DNA.OL15
> > forcefield the structure is moving more towards B-conformation at the end
> > of the run. Thus, I want to know which would be the appropriate
> forcefield
> > to study the formation of Z-DNA. Thank you.
> >
> >
> >
> >
> > *Thanks & Regards,*
> >
> > *Yogeeshwar Ajjugal*
> >
> > *Ph.D ScholarC/O Dr.Thenmalarchelvi Rathinavelan*
> >
> >
> > *Dept Of Biotechnology,Indian Institute of Technology Hyderabad,*
> > *Kandi, Medak-502285.*
> >
> > On Tue, Jan 24, 2017 at 5:31 PM, Yogeeshwar Ajjugal <
> > bo14resch11004.iith.ac.in> wrote:
> >
> > > Dear jiri Sponer,
> > >
> > > Thank you for your explanation. I have done with explicit simulations
> > and
> > > observed mainly backbone torsion angles
> > > (ε,z,α,γ) changing to B-form.
> > >
> > > *Thanks & Regards,*
> > >
> > > *Yogeeshwar Ajjugal*
> > >
> > > *Ph.D ScholarC/O Dr.Thenmalarchelvi Rathinavelan*
> > >
> > >
> > > *Dept Of Biotechnology,Indian Institute of Technology Hyderabad,*
> > > *Kandi, Medak-502285.*
> > >
> > > On Tue, Jan 24, 2017 at 3:42 PM, Jiri Sponer <sponer.ncbr.muni.cz>
> > wrote:
> > >
> > >> It is somewhat unclear, what do you mean by complete transformation
> > >> of Z-form to B-form? I think this has never been achieved by MD except
> > >> of enhanced sampling methods, as it requires syn - anti flips etc.
> > >> To get Z to B transition in MD spontaneosly would be a milestone.
> > >>
> > >> About Z-form, it in general requires (in experiment) specific
> > >> "environmental" conditions. Under normal conditions, B form is
> > >> preferred over Z-form for any sequence, however, due to complexity
> > >> of the transition, the transition is not supposed to be observable in
> > >> MD.
> > >>
> > >> Was it explicit solvent simulation?
> > >>
> > >> Jiri
> > >>
> > >> -------------------------------------------------------
> > >> Jiri Sponer
> > >> Professor of Biochemistry
> > >> Head of Department of Structure and Dynamics of Nucleic Acids
> > >> Institute of Biophysics
> > >> Academy of Sciences of the Czech Republic
> > >> Kralovopolska 135
> > >> CZ-61265 Brno
> > >> Czech Republic
> > >> e-mail: sponer.ncbr.muni.cz
> > >> fax: 420 5412 12179
> > >> phone: 420 5415 17133
> > >> http://www.ibp.cz/
> > >> http://www.ibp.cz/en/departments/structure-and-
> > dynamics-of-nucleic-acids/
> > >> -----------------------------------------------------------
> > >>
> > >>
> > >>
> > >>
> > >> On Tue, 24 Jan 2017, Yogeeshwar Ajjugal wrote:
> > >>
> > >> > Date: Tue, 24 Jan 2017 15:23:24 +0530
> > >> > From: Yogeeshwar Ajjugal <bo14resch11004.iith.ac.in>
> > >> > Reply-To: AMBER Mailing List <amber.ambermd.org>
> > >> > To: AMBER Mailing List <amber.ambermd.org>
> > >> > Subject: [AMBER] Regarding forcefields for Z-DNA
> > >> >
> > >> > Dear amber users,
> > >> >
> > >> > I have performed GPU MD simulations using 2 force fields for Z-DNA
> > >> protein
> > >> > complex , namely 1) ff99SB and 2) combined force field of DNA
> > >> > (leaprc.DNA.OL15) and protein (leaprc.protein.ff14SB) of AMBER16. I
> > >> observe
> > >> > that in ff99SB simulations the Z-DNA conformation remains unchanged
> > >> > whereas, in leaprc.DNA.OL15 specified simulations the conformation
> of
> > >> Z-DNA
> > >> > is completely transformed to B-DNA conformation. Hence, which of
> > these
> > >> > results is reliable? What should be the appropriate force field to
> > study
> > >> > Z-DNA conformation? It would be really helpful if you could help me
> > out
> > >> > with this issue. Thank you very much.
> > >> >
> > >> > *Thanks & Regards,*
> > >> >
> > >> > *Yogeeshwar Ajjugal*
> > >> >
> > >> > *Ph.D ScholarC/O Dr.Thenmalarchelvi Rathinavelan*
> > >> >
> > >> >
> > >> > *Dept Of Biotechnology,Indian Institute of Technology Hyderabad,*
> > >> > *Kandi, Medak-502285.*
> > >> > _______________________________________________
> > >> > AMBER mailing list
> > >> > AMBER.ambermd.org
> > >> > http://lists.ambermd.org/mailman/listinfo/amber
> > >> >
> > >>
> > >> _______________________________________________
> > >> AMBER mailing list
> > >> AMBER.ambermd.org
> > >> http://lists.ambermd.org/mailman/listinfo/amber
> > >>
> > >
> > >
> > _______________________________________________
> > AMBER mailing list
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> >
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Received on Wed Feb 01 2017 - 02:00:02 PST
