Unfortunately, the original question was so poorly formulated
that it was not fully understandable. OL15 is definitely the
best what is currently available for Z-DNA, though it is obviously
not flawless, due to the general force-field approximation.
Z-DNA is an intrisically strained structure, with quite tortured
backbone and very complex combination of dihedrals (from the point of view
of the electronic structure), thus a difficult goal for force fields.
Note that if an instability is seen in protein-NA complexes,
it can be due the prot-NA interface as well as strains in the
starting structure. For a general recipe see
Can We Execute Stable Microsecond-Scale Atomistic Simulations of
Protein-RNA Complexes?
By: Krepl, M.; Havrila, M.; Stadlbauer, P.; et al.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION Volume: 11 Issue: 3
Pages: 1220-1243 Published: MAR 2015
and a follow up here:
http://onlinelibrary.wiley.com/doi/10.1002/wrna.1405/full
Though it is for RNA-protein complexes, the experiecne should
be transferable also for DNA-protein complexes. There are 100+
things that may happen in protein-NA simulations, even when using
good atomistic experimental data as the start.
Best wishes, Jiri
On Wed, 1 Feb 2017, Josh Berryman wrote:
> Date: Wed, 1 Feb 2017 10:38:24 +0100
> From: Josh Berryman <the.real.josh.berryman.gmail.com>
> Reply-To: AMBER Mailing List <amber.ambermd.org>
> To: AMBER Mailing List <amber.ambermd.org>
> Subject: Re: [AMBER] Regarding forcefields for Z-DNA
>
> 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
>>>>>>
>>>>>
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>>>>
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Received on Sat Feb 04 2017 - 03:30:02 PST
