VMD-L Mailing List

From: Francesco Pietra (chiendarret_at_gmail.com)
Date: Sun Apr 04 2021 - 08:53:46 CDT

I never used constant pH MD, although I was aware of NAMD implementation of
it.
The reason to investigate HIS protonation was twofold: the overwhelmingly
presence of nucleosides and the two recent papers mentioned on previous
posts in this thread, where constant HIS protonation was used and the
various possible states explored by MD. Why they did not take the shorter
route of constant pH MD? The authority of the authors let me think that
constant pH MD is no panacea.

francesco

On Sun, Apr 4, 2021 at 2:28 AM Miro Astore <miro.astore_at_gmail.com> wrote:

> You might consider constant ph simulations? They're supported in namd.
>
> On Sat., 3 Apr. 2021, 6:43 pm Francesco Pietra, <chiendarret_at_gmail.com>
> wrote:
>
>> Hi Josh and James
>> I had already seen another checking the MD stability for the various
>> protonation states of HIS:
>>
>> Histidine protonation and the activation of viral fusion proteins,
>> Daniela S. Mueller, Thorsten Kampmann, Ragothaman Yennamalli, Paul R.
>> Young, Bostjan Kobe
>> and Alan E. Mark, Biochemical Society Transactions (2008) Volume 36, part
>> 1
>>
>> With so many HISs as in my case, the combinations scale tremendously up
>> and one fears to miss the most important overall state.
>> There is a need of new software to assign the protonation states of HIS.
>> Also, if there is a fine tuning of HSE vs HSD, changeable during MD in
>> response to the interaction with the strongly negative electrostatics of
>> the nucleosides, things become complicated indeed.
>>
>> But I'll read James' paper and I'll try the suggested Propka and
>> DelphiPKa, if not else to see the output.
>>
>> What about the famous ROSETTA? Perhaps, however, it just uses Propka or
>> Delphi PKa.
>>
>> thanks
>> francesco
>>
>> On Sat, Apr 3, 2021 at 1:35 AM Vermaas, Josh <vermaasj_at_msu.edu> wrote:
>>
>>> Admittedly, it has been a while since I looked at propka output in
>>> detail, but when I run regular proteins through pdb2pqr (
>>> https://urldefense.com/v3/__https://server.poissonboltzmann.org/__;!!DZ3fjg!utaPrsS_gsFHwXNH7Hpzef2KUahVtzm0kampwW1tuWo2rJQPH6NWYdASvkhmXMr3KA$
>>> <https://urldefense.com/v3/__https://server.poissonboltzmann.org/__;!!DZ3fjg!tsqIFHVKijNxX_B1fbFz9jygI2pMsbnGZC8el-7pPOZ9fT3WcvW5y8s__expakzqDA$>),
>>> it claims to use PropKa to assign charges, and the pqr files that come out
>>> definitely seem to have a made an attempt to choose between HSD and HSE, so
>>> I assume there is something in the PropKa output that it is using to
>>> determine histidine protonation. For the applications I was using it for,
>>> this level of detail has been fine, but JC is right, you can also just try
>>> all protonation state combinations and see what makes sense.
>>>
>>>
>>>
>>> -Josh
>>>
>>>
>>>
>>> *From: *"Gumbart, JC" <gumbart_at_physics.gatech.edu>
>>> *Date: *Friday, April 2, 2021 at 4:43 PM
>>> *To: *"Vermaas, Josh" <vermaasj_at_msu.edu>
>>> *Cc: *Francesco Pietra <chiendarret_at_gmail.com>, VMD Mailing List <
>>> vmd-l_at_ks.uiuc.edu>, "henin_at_ibpc.fr" <henin_at_ibpc.fr>, "zhu13_at_llnl.gov" <
>>> zhu13_at_llnl.gov>
>>> *Subject: *Re: vmd-l: histidine protonation
>>>
>>>
>>>
>>> I’m not sure about DelphiPka, but Propka doesn’t tell you which nitrogen
>>> to put the proton on. We found running simulations of different states and
>>> checking their stability to be the most reliable (albeit more
>>> time-consuming) way to assign protons to histidines:
>>> https://urldefense.com/v3/__https://pubs.rsc.org/en/content/articlelanding/2021/sc/d0sc04942e__;!!DZ3fjg!utaPrsS_gsFHwXNH7Hpzef2KUahVtzm0kampwW1tuWo2rJQPH6NWYdASvkjQspYApg$
>>> <https://urldefense.com/v3/__https:/pubs.rsc.org/en/content/articlelanding/2021/sc/d0sc04942e__;!!HXCxUKc!gvFYR3OpPr1fjuH1jJQ1NtrWmWfgzesHlw-bJ5W_WnlWlHNPuvfRXD9_XBJvm84$>
>>>
>>>
>>>
>>> We ran for 20 ns x 3, but you can often see a disruption sooner.
>>>
>>>
>>>
>>> Best,
>>>
>>> JC
>>>
>>>
>>>
>>> On Apr 2, 2021, at 2:26 PM, Vermaas, Josh <vermaasj_at_msu.edu> wrote:
>>>
>>>
>>>
>>> Hi Francesco,
>>>
>>>
>>>
>>> Propka (https://urldefense.com/v3/__https://github.com/jensengroup/propka__;!!DZ3fjg!utaPrsS_gsFHwXNH7Hpzef2KUahVtzm0kampwW1tuWo2rJQPH6NWYdASvkg09wjw8Q$
>>> <https://urldefense.com/v3/__https:/github.com/jensengroup/propka__;!!DZ3fjg!qLqvG5aUIsZadcvLdv2KKVS99Ta3HEX53KL7IdL8pM3CNQJ6bPm9CzlpqFDRl_oZJA$>)
>>> or DelphiPka (https://urldefense.com/v3/__https://github.com/delphi001/DelphiPka__;!!DZ3fjg!utaPrsS_gsFHwXNH7Hpzef2KUahVtzm0kampwW1tuWo2rJQPH6NWYdASvkg54RyCNg$
>>> <https://urldefense.com/v3/__https:/github.com/delphi001/DelphiPka__;!!DZ3fjg!qLqvG5aUIsZadcvLdv2KKVS99Ta3HEX53KL7IdL8pM3CNQJ6bPm9CzlpqFCAQcr_zA$>)
>>> in principle should be able to handle non-protein ionizable groups.
>>>
>>>
>>>
>>> -Josh
>>>
>>>
>>>
>>> *From: *<owner-vmd-l_at_ks.uiuc.edu> on behalf of Francesco Pietra <
>>> chiendarret_at_gmail.com>
>>> *Date: *Friday, April 2, 2021 at 1:36 PM
>>> *To: *VMD Mailing List <vmd-l_at_ks.uiuc.edu>, "henin_at_ibpc.fr" <
>>> henin_at_ibpc.fr>, "zhu13_at_llnl.gov" <zhu13_at_llnl.gov>
>>> *Subject: *vmd-l: histidine protonation
>>>
>>>
>>>
>>> Hi
>>>
>>> I am faced with the problem of establishing the protonation status of
>>> many histidine residues present in a nucleic acid-protein ensemble, both
>>> inside and on the periphery. All that in the framework of CHARMM36 for NAMD
>>> MD.
>>>
>>>
>>>
>>> Servers for direct assignment, like H++, are useless because of the
>>> presence of nucleic acids.
>>>
>>>
>>>
>>> I came across two interesting old posts by Zhu and Henin to this concern
>>> and wonder whether there is anything additionally useful for the above
>>> ensemble
>>>
>>> *From:* Fangqiang Zhu (*fzhu_at_ks.uiuc.edu*
>>> <fzhu_at_ks.uiuc.edu?Subject=Re:%20%20how%20can%20I%20know%20which%20type%20HIS%20belong%20to?(HSD,HSE,HSP)>
>>> )
>>> *Date:* Sat Nov 29 2003 - 00:22:03 CST
>>>
>>> *From:* Jérôme Hénin (*jerome.henin_at_uhp-nancy.fr*
>>> <jerome.henin_at_uhp-nancy.fr?Subject=Re:%20%20how%20can%20I%20know%20which%20type%20HIS%20belong%20to?(HSD,HSE,HSP)>
>>> )
>>> *Date:* Sat Nov 29 2003 - 04:37:30 CST
>>>
>>> Thanks for advice
>>>
>>> francesco pietra
>>>
>>>
>>>
>>