Just short comment. One has to differentiate between
INTRINSIC stacking (potential energy surface) and free energies of
stacking, i.e., population of stacked vs. unstacked, which
is a results of numerous energy terms, not just the direct base
to base (intrinsic) interactions.
These are VERY different physical-chemistry processes.
Free energies of stacking typically do not correlate well
with potential energies of stacking.
I spent years with benchmark QM calculations, and to my opinion
AMBER does reasonably well for the intrinsic base stacking.
We currently work on a new QM benchmark (ms in revision), no
dramatic change of the overall picture.
Some minireview is here:
Nature and Magnitude of Aromatic Base Stacking in DNA and RNA: Quantum
Chemistry, Molecular Mechanics, and Experiment
Sponer et al.. BIOPOLYMERS, 99, 978-988, 2013
We have commented also here
RNA Structural Dynamics As Captured by Molecular Simulations: A
Comprehensive Overview, Sponer, Bussi et al. CHEMICAL REVIEWS, 118,
4177-4338, 2018
I think there is nothing like universal "over-estimation" of stacking
in nucleic acids. Some stacking patterns are probably over-stabilized
while others are under-stabilized, in a context-dependent manner.
In case of benzene-benzene type of complexes,
vdW favors perfect stacking which is, however, unstable due
to molecular quadrupole - molecular quadrupole interaction,
this causes the parallel-displaced a T-shape arrangements.
Base stacking electrostatics has molecular dipole - molecular dipole
nature.
Base-base and deoxyribose-base stacking interactions in B-DNA and
Z-DNA: A quantum-chemical study Sponer et al, BIOPHYS. J. 73, 76-87, 1997
However, solvent screening counterbalances the electrostatics at
the Potential of mean force level of description
Thermodynamic parameters for stacking and hydrogen bonding of nucleic acid
bases in aqueous solution: Ab initio/Langevin dipoles study
Florian et al. J PHYS CHEM B, 103, 884-892, 1999
So, stacking is quite a complex phenomenon and its description requires
balanced description of not only the direct interaction but also
of the context, the latter is often the problem.
Best wishes, Jiri
On Fri, 19 Oct 2018, Carlos Simmerling wrote:
> Date: Fri, 19 Oct 2018 17:21:48 -0400
> From: Carlos Simmerling <carlos.simmerling.gmail.com>
> Reply-To: AMBER Mailing List <amber.ambermd.org>
> To: AMBER Mailing List <amber.ambermd.org>
> Subject: Re: [AMBER] pi-pi And Aromatic Interactions
>
> Oh you might have a very good point about it not being sufficient! I just
> meant that there's reason to think it's at least partly there.
>
> On Fri, Oct 19, 2018, 5:15 PM Chris Neale <candrewn.gmail.com> wrote:
>
>> Good point. I didn't realize that was sufficient.
>>
>> On Fri, Oct 19, 2018 at 3:03 PM Carlos Simmerling <
>> carlos.simmerling.gmail.com> wrote:
>>
>>> I think that might be true if it were only vdw, but don't forget that
>> these
>>> atoms have partial charges and the rings have quadrupoles. The inner
>> parts
>>> of the ring are substantially negative compared to the outer edge atoms
>> (eg
>>> for a benzene or Phe). The indeed gives a favorable cation-pi
>> interaction,
>>> and will influence relative energies of T vs stacked geometries. Of
>> course
>>> the level of accuracy is open to debate, but the terms aren't completely
>>> absent.
>>>
>>> On Fri, Oct 19, 2018, 4:38 PM Chris Neale <candrewn.gmail.com> wrote:
>>>
>>>> Should VDW not (incorrectly) favor in-register-parallel over
>>>> parallel-displaced and T-shaped geometries for aromatic rings?
>>>> http://www.jbc.org/content/273/25/15458.long
>>>>
>>>> And how does the Hamiltonian at all account for cation-pi?
>>>>
>>>> I do agree that other parts of the force field might lead to
>>> configurations
>>>> that are stabilized by pi-based interactions in real life though not in
>>>> simulation, and that disrupting the associated pi-based interaction may
>>>> thereby have an experimental effect.
>>>>
>>>>
>>>>
>>>>
>>>>
>>>> On Fri, Oct 19, 2018 at 6:50 AM Christina Bergonzo <
>> cbergonzo.gmail.com>
>>>> wrote:
>>>>
>>>>> Hi,
>>>>>
>>>>> I wanted to give a more nuanced look at the pi-pi and cation-pi
>>>> interaction
>>>>> in MD force fields.
>>>>>
>>>>> While there is no explicit force field term for pi-pi or cation-pi
>>>>> interactions, you can of course look for their effects, which are
>>> indeed
>>>>> represented using MD - otherwise my DNA duplexes would be in trouble!
>>>>> Force fields rely on van der Waals to pick up the effects of these
>>>>> interactions, and generally they can capture those effects - of
>> course,
>>>>> this is modulated by the desired level of accuracy.
>>>>>
>>>>> You can take a look at these papers to get an understanding of the
>>> issue
>>>>> w.r.t. QM:
>>>>> https://www.ncbi.nlm.nih.gov/pubmed/22260616
>>>>>
>> https://link.springer.com/content/pdf/bbm%3A978-3-319-15382-7%2F1.pdf
>>>>>
>>>>> Here is an example where we measured base eversion pathways, noted a
>>>>> cation-pi interaction, and experimental collaborators made the
>> mutation
>>>> to
>>>>> disrupt it, causing catalytic activity of the protein with an
>>> (aromatic)
>>>>> damaged DNA base to decrease, but leaving the activity of the
>>>>> (non-aromatic) apurinic damage intact:
>>>>> https://academic.oup.com/nar/article/44/2/683/2468125
>>>>>
>>>>> And here is an example of base stacking in RNA, where it is argued
>> that
>>>>> pi-pi stacking is overstabilized:
>>>>> http://www.pnas.org/content/110/42/16820
>>>>>
>>>>>
>>>>
>>>
>> http://www.pnas.org/content/pnas/suppl/2013/09/11/1309392110.DCSupplemental/pnas.201309392SI.pdf
>>>>>
>>>>>
>>>>> For analysis of these types of interactions, I would make sure to
>> look
>>> at
>>>>> not only the energies but also the distances and geometries of pi-pi
>> or
>>>>> cation-pi binding pairs.
>>>>>
>>>>> Hope this helps,
>>>>> Christina
>>>>>
>>>>> On Thu, Oct 18, 2018 at 11:27 PM Chris Neale <candrewn.gmail.com>
>>> wrote:
>>>>>
>>>>>> Be careful... atomistic force fields typically don't have any pi
>>>> electron
>>>>>> effects in the Hamiltonian, so why would you analyze for them? In
>>> fact,
>>>>>> most atomistic force fields do a pretty terrible job at pi-based
>>>> effects
>>>>>> like aromatic stacking. Same goes for cation-pi interactions.
>>>>>>
>>>>>> On Thu, Oct 18, 2018 at 8:08 PM Meng Wu <
>> wumeng.shanghaitech.edu.cn>
>>>>>> wrote:
>>>>>>
>>>>>>> Dear all,
>>>>>>>
>>>>>>> I have MD for my channel protein and substrate molecules and
>> I
>>>> have
>>>>>>> used the "lie" command to calculate the EELEC and EVDW terms.
>> Now I
>>>>> want
>>>>>> to
>>>>>>> analysis like the pi-pi interactions or aromatic interactions
>>> between
>>>>> the
>>>>>>> substrates and protein & residue to residue in protein, could
>>> anybody
>>>>>> give
>>>>>>> me some suggestions? Thank you in advance!
>>>>>>>
>>>>>>> Best regards,
>>>>>>> Meng Wu
>>>>>>>
>>>>>>> _______________________________________________
>>>>>>> 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
>>>>>>
>>>>>
>>>>>
>>>>> --
>>>>> --------------------------------------------------------------
>>>>> Christina Bergonzo
>>>>> Research Chemist
>>>>> NIST/IBBR NRC Postdoctoral Researcher
>>>>> --------------------------------------------------------------
>>>>> _______________________________________________
>>>>> AMBER mailing list
>>>>> AMBER.ambermd.org
>>>>> http://lists.ambermd.org/mailman/listinfo/amber
>>>>>
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Received on Fri Oct 19 2018 - 16:00:02 PDT
