[gmx-developers] Contributing new water models

[David van der Spoel]

On 2014-05-31 06:29, Lee-Ping Wang wrote:
> Hi David,
>
> Thank you for the suggestions.  I understand that increasing protein stability isn't necessarily a good thing; mainly I meant to say that the TIP3P-FB water model doesn't unfold the protein. :)  Looking at protein stability only has the ability to determine whether the force field is behaving badly, but it can't tell us whether it's behaving well.
>
> I agree it would be good to look at residual dipolar couplings in our protein force field validations.  Can you explain what you meant by the solvation free energy?  Would that be the solvation free energy of the whole protein, or individual amino acids / side chain analogues?
>
I did mean side chain analogs, like Berk Hess, David Mobley and others 
have done.
> Thanks,
>
> - Lee-Ping
>
> On May 30, 2014, at 9:12 AM, David van der Spoel <spoel at xray.bmc.uu.se> wrote:
>
>> On 2014-05-30 10:37, Lee-Ping Wang wrote:
>>> Hi Mark,
>>>
>>> Thank you, I appreciate it very much. :)
>>>
>>> I understand it’s important not to give users too many options in
>>> pdb2gmx that could lead to incorrect results.  Kyle Beauchamp and I are
>>> working on a manuscript that tests a grid of available protein force
>>> fields in Gromacs vs. several water models, including my contribution.
>>> So far we have found that changing TIP3P -> TIP3P-FB increases protein
>>> stability (i.e. decreases alpha-carbon RMSD to the crystal structure)
>>> for 15 different proteins, improves NMR J-coupling prediction in over
>>> 400 small tripeptides, and improves chemical shift prediction in
>>> lysozyme and ubiquitin.  We ran these tests for ff96, ff99sb,
>>> ff99sb-ildn and ff99sb-nmr; also we haven’t tested any properties where
>>> TIP3P-FB makes the model worse.  This isn’t published yet.
>>>
>> Note that increased stability is not necessarily a good thing. It is rather the balance between stability and dynamics. You could also consider doing free energy of solvation calculations, don't forget the temperature dependence. The NMR data point to real improvements though. You could also consider RDCs.
>>
>>
>>> If we publish improved results for most of the protein force fields +
>>> the new water models, then I might request that the new models be
>>> considered for addition to pdb2gmx. We could evaluate whether that
>>> decision is appropriate at that future time. Let me know what you think.
>>>
>>> -Lee-Ping
>>>
>>> *From:*gromacs.org_gmx-developers-bounces at maillist.sys.kth.se
>>> [mailto:gromacs.org_gmx-developers-bounces at maillist.sys.kth.se] *On
>>> Behalf Of *Mark Abraham
>>> *Sent:* Friday, May 30, 2014 12:35 AM
>>> *To:* Discussion list for GROMACS development
>>> *Subject:* Re: [gmx-developers] Contributing new water models
>>>
>>> Hi Lee-Ping,
>>>
>>> That sounds useful. Generally we will only incorporate force field
>>> things that are published, so that is good. I'm hesitant to make them
>>> available with pdb2gmx -water, lest it be too easy for people to misuse
>>> them with an inappropriate force field. Incorporating the atom types
>>> into the tested force fields and making the .itp files available with
>>> them sounds fine to me. Then a quick sed -i will replace whatever was
>>> selected with pdb2gmx.
>>>
>>> Mark
>>>
>>> On May 28, 2014 7:12 PM, "Lee-Ping Wang" <leeping at stanford.edu
>>> <mailto:leeping at stanford.edu>> wrote:
>>>
>>> Dear developers,
>>>
>>> I'd like to contribute the following water models that were published in
>>> our recent article, "Building force fields - a systematic, automatic and
>>> reproducible approach."  The models, called TIP3P-FB and TIP4P-FB, are
>>> reparameterized versions of the TIP3P and TIP4P models; they have
>>> identical functional forms and computational cost, just different
>>> parameters.  They are highly accurate for reproducing the thermodynamic,
>>> kinetic and structural properties of liquid water across a wide
>>> temperature and pressure range.  The .itp files are attached in their
>>> final form.
>>>
>>> I've run several microseconds of protein simulations using TIP3P-FB and
>>> TIP4P-FB, and they are highly compatible with the AMBER protein force
>>> fields (more specifically, amber99sb, amber99sb-ildn and amber99sb-nmr).
>>>   In fact, replacing TIP3P with TIP3P-FB tends to improve the stability
>>> of the "fast folding" proteins in D.E. Shaw's paper, and it also
>>> improves the prediction of NMR J-couplings and chemical shifts.  This is
>>> currently unpublished work but I'm working on a manuscript.
>>>
>>> Please let me know if there's interest.  I think it could make sense to
>>> bundle this with the main Gromacs distribution, because the water models
>>> come with atom types that need to go into "ffnonbonded.itp" for the
>>> various implemented force fields.
>>>
>>> Thanks,
>>>
>>> - Lee-Ping Wang
>>>
>>> Link to the paper:
>>> https://www.dropbox.com/s/phwlr3jsnhe46bw/Wang_Pande.RigidWater.JPCL.2014.pdf
>>>
>>>
>>>
>>>
>>> --
>>> Gromacs Developers mailing list
>>>
>>> * Please search the archive at
>>> http://www.gromacs.org/Support/Mailing_Lists/GMX-developers_List before
>>> posting!
>>>
>>> * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
>>>
>>> * For (un)subscribe requests visit
>>> https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-developers
>>> or send a mail to gmx-developers-request at gromacs.org
>>> <mailto:gmx-developers-request at gromacs.org>.
>>>
>>>
>>>
>>
>>
>> --
>> David van der Spoel, Ph.D., Professor of Biology
>> Dept. of Cell & Molec. Biol., Uppsala University.
>> Box 596, 75124 Uppsala, Sweden. Phone:	+46184714205.
>> spoel at xray.bmc.uu.se    http://folding.bmc.uu.se
>> --
>> Gromacs Developers mailing list
>>
>> * Please search the archive at http://www.gromacs.org/Support/Mailing_Lists/GMX-developers_List before posting!
>>
>> * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
>>
>> * For (un)subscribe requests visit
>> https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-developers or send a mail to gmx-developers-request at gromacs.org.
>


-- 
David van der Spoel, Ph.D., Professor of Biology
Dept. of Cell & Molec. Biol., Uppsala University.
Box 596, 75124 Uppsala, Sweden. Phone:	+46184714205.
spoel at xray.bmc.uu.se    http://folding.bmc.uu.se