From: Vermaas, Josh (
Date: Fri Apr 02 2021 - 18:35:53 CDT

Admittedly, it has been a while since I looked at propka output in detail, but when I run regular proteins through pdb2pqr (;!!DZ3fjg!ueoUtt97XwFi-Z5W849k_aqhuWX9q-qmMefcRYBWp_-f18O27fHeVpVC9cxsuJL9Lw$ ), 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.


From: "Gumbart, JC" <>
Date: Friday, April 2, 2021 at 4:43 PM
To: "Vermaas, Josh" <>
Cc: Francesco Pietra <>, VMD Mailing List <>, "" <>, "" <>
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:;!!DZ3fjg!ueoUtt97XwFi-Z5W849k_aqhuWX9q-qmMefcRYBWp_-f18O27fHeVpVC9cwD5azSYA$ <;!!HXCxUKc!gvFYR3OpPr1fjuH1jJQ1NtrWmWfgzesHlw-bJ5W_WnlWlHNPuvfRXD9_XBJvm84$>

We ran for 20 ns x 3, but you can often see a disruption sooner.


On Apr 2, 2021, at 2:26 PM, Vermaas, Josh <<>> wrote:

Hi Francesco,

Propka (;!!DZ3fjg!ueoUtt97XwFi-Z5W849k_aqhuWX9q-qmMefcRYBWp_-f18O27fHeVpVC9cyK7jn7Kg$ <;!!DZ3fjg!qLqvG5aUIsZadcvLdv2KKVS99Ta3HEX53KL7IdL8pM3CNQJ6bPm9CzlpqFDRl_oZJA$>) or DelphiPka (;!!DZ3fjg!ueoUtt97XwFi-Z5W849k_aqhuWX9q-qmMefcRYBWp_-f18O27fHeVpVC9cxyJJ7daA$ <;!!DZ3fjg!qLqvG5aUIsZadcvLdv2KKVS99Ta3HEX53KL7IdL8pM3CNQJ6bPm9CzlpqFCAQcr_zA$>) in principle should be able to handle non-protein ionizable groups.


From: <<>> on behalf of Francesco Pietra <<>>
Date: Friday, April 2, 2021 at 1:36 PM
To: VMD Mailing List <<>>, "<>" <<>>, "<>" <<>>
Subject: vmd-l: histidine protonation

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 (<,HSE,HSP)>)
Date: Sat Nov 29 2003 - 00:22:03 CST
From: Jérôme Hénin (<,HSE,HSP)>)
Date: Sat Nov 29 2003 - 04:37:30 CST
Thanks for advice
francesco pietra