Thanks for your help. I have to go through the tutorials.
*With regards,*
*Dulal Mondal,*
*Research Scholar,*
*Department of Chemistry,*
*IIT Kharagpur, Kharagpur 721302.*
On Fri, 29 Aug, 2025, 11:59 pm Erika McCarthy, <em989.chem.rutgers.edu>
wrote:
> Hi Dulal,
>
> In the tutorial you are following, it seems they are manually building the
> endstates and assigning charges. They build the deprotonated state based on
> the protonated one by changing the charges in tleap. It seems to me the
> tutorial is saying the VDW is "fortunately set to zero" because then they
> don't manually have to change the VDW radius from the protonated state. I
> see how that could be confusing though, because it could seem as if
> softcore potentials do not handle the VDW parameter. If you want to follow
> this tutorial, I think you would need to set the VDW for the dummy H in the
> deprotonated state to be zero using parmed after you have run tleap. Then
> it will be scaled from the protonated value to zero over the TI simulation.
>
> This sort of pKa simulation is very similar to a relative binding free
> energy calculation (like in tutorials 7.1 and 7.2) where a ligand is
> modified, except here a proton is disappearing. If you wanted to leverage
> some advanced methods from those tutorials, you could consider
> parameterizing your deprotonated state to obtain a .lib file with
> consistent atom names for each, building them each in tleap, then using
> timerge in parmed to generate a dual topology. Hope that helps!
>
> Best regards,
> Erika McCarthy
> ------------------------------
> *From:* Dulal Mondal via AMBER <amber.ambermd.org>
> *Sent:* Friday, August 29, 2025 9:38 AM
> *To:* AMBER Mailing List <amber.ambermd.org>
> *Subject:* [AMBER] pKa through TI calculation
>
> Dear Experts,
>
> I am following the tutorial
>
> https://nam02.safelinks.protection.outlook.com/?url=https%3A%2F%2Fambermd.org%2Ftutorials%2Fadvanced%2Ftutorial6%2Findex.php&data=05%7C02%7Cem989%40chem.rutgers.edu%7C17477273cc3d4dd907b008dde7017b46%7Cb92d2b234d35447093ff69aca6632ffe%7C1%7C0%7C638920715734676448%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=JMgk81YuoMisbiwjV7ZdkrLsEE7pLMDSZvMxsXfMrmY%3D&reserved=0
> <https://ambermd.org/tutorials/advanced/tutorial6/index.php>
>
> In this tutorial, they describe the Asp residue, for which the VDW terms of
> the hydroxyl hydrogen are fortunately set to zero.
>
> I want to calculate the free energy difference between protonated Lys and
> deprotonated Lys. However, for the hydrogens bound to nitrogen, the VDW
> parameters are *not zero*. Should I explicitly modify the VDW parameters in
> the deprotonated Lys prmtop file?
>
> --
> *With regards,*
> *Dulal Mondal,*
> *Research Scholar,*
> *Department of Chemistry,*
> *IIT Kharagpur, Kharagpur 721302.*
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
>
> https://nam02.safelinks.protection.outlook.com/?url=http%3A%2F%2Flists.ambermd.org%2Fmailman%2Flistinfo%2Famber&data=05%7C02%7Cem989%40chem.rutgers.edu%7C17477273cc3d4dd907b008dde7017b46%7Cb92d2b234d35447093ff69aca6632ffe%7C1%7C0%7C638920715734715750%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=0GahI8fFo5hjcqCKlFgQk%2FsHT9sJQbo4rjdzxIdA5kE%3D&reserved=0
> <http://lists.ambermd.org/mailman/listinfo/amber>
>
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Fri Aug 29 2025 - 12:00:03 PDT
