[gmx-users] pH

[Justin Lemkul]

On 6/29/15 11:04 AM, Atila Petrosian wrote:
> Dear Erik
>
> Thanks for your reply,
>
> I have another question. By default, Gromacs considers physiological pH
> value (7), am I right?
>
> Based on experimental data, my project should do under the asidic pH (2).
>
> You mentioned to pka. Should I use henderson hasselbalch equation?
>
> pH = Pka + log ([A-]/[HA]) for acids
> pH = Pka + log ([B]/[BH+]) for bases
>
> For amino acid Lysine (K) with pka = 10.53 ~ 11
> for side chain (for simplicity, I rounded the value),
>
> 2 = 11 + log ([B]/[BH+]) ===> [BH+] = (anti log 9) [B]
>
> Thus, when I use following command
>
> pdb2gmx -f *.pdb -lys
>
> gromacs ask me:
>
> Which LYSINE type do you want for residue 14
> 0. Not protonated (charge 0) (LYN)
> 1. Protonated (charge +1) (LYS)
>
> I select 1 (Protonated)
>
> Is my rationalization true?
> ---------------------------------------------------------------------------------------------------
>
> and for amino acid Aspartic acid (ASP) with pka = 3.86 ~ 4
> for side chain (for simplicity, I rounded the value),
>
> 2 = 4 + log ([A-]/[HA]) ===> [HA] = (antilog 2) [A-]
>
> Thus, when I use following command
>
> pdb2gmx -f *.pdb -asp
>
> gromacs ask me:
>
> Which ASPARTIC ACID type do you want for residue 18
> 0. Not protonated (charge -1) (ASP)
> 1. Protonated (charge 0) (ASH)
>
> I select 1 (Protonated)
>
> Is my rationalization true?
> ---------------------------------------------------------------------------------------------------
>
> If I am wrong, please guide me.
>

The microenvironment of an individual residue can significantly alter the pKa 
away from its canonial value.  In some enzymes, catalytic Lys is in a 
hydrophobic pocket with a pKa of approximately 4!  One needs to do thorough 
calculations of what the pKa values should be in a given protein.  There are 
many programs, servers, etc that do this.

-Justin

-- 
==================================================

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalemkul at outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

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