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
> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
>
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Sat Jan 28 2017 - 12:30:03 PST
