In general, I tend to avoid the "pi-pi" terminology for stacking, as it
gives a false impression that some fundamental "pi" terms are missing
in the force field. In fact, the correspondence between QM and MM PESs
indicates absence of any dramatic "pi" terms. LJ term with
atom-centered ESP charges works quite well.
Kollman's original PES idea was brilliant. I remember, when making
the first electron correlation calculations on stacking in 1995-1996, we
were shocked by inability to find any significant MM failure
(described in Hobza&Sponer ChemRev 1999, still valid until today).
There has been recent atempts to "complicate" the QM base stacking
picture by various energy decompositions (such as SAPT), but
I am not in favor of such interpretations, as all these sophisticated
energy terms typically have exponential behavior with respect
to interatomic distances and effectively compensate each other.
So a sort of "false-positive" claims. LJ potential effectively
includes the sum of all these terms very well.
Large-scale compensation of errors in pairwise-additive empirical force
fields: comparison of AMBER intermolecular terms with rigorous DFT-SAPT
calculations, Zgarbova et al. PHYS CHEM CHEM PHYS 12, 10476-10493, 2010
The relative errors of MM for medium-strength H-bonds are much
larger.
Sorry for long contributions. Jiri
On Sat, 20 Oct 2018, Jiri Sponer wrote:
> Date: Sat, 20 Oct 2018 00:56:19 +0200 (MEST)
> From: Jiri Sponer <sponer.ncbr.muni.cz>
> Reply-To: AMBER Mailing List <amber.ambermd.org>
> To: AMBER Mailing List <amber.ambermd.org>
> Subject: Re: [AMBER] pi-pi And Aromatic Interactions
>
> 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
>>>>>>>>
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>>>>>>> _______________________________________________
>>>>>>> AMBER mailing list
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>>>>>>>
>>>>>>
>>>>>>
>>>>>> --
>>>>>> --------------------------------------------------------------
>>>>>> Christina Bergonzo
>>>>>> Research Chemist
>>>>>> NIST/IBBR NRC Postdoctoral Researcher
>>>>>> --------------------------------------------------------------
>>>>>> _______________________________________________
>>>>>> AMBER mailing list
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>>>>>>
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Received on Fri Oct 19 2018 - 16:30:02 PDT
