[gmx-users] Doubt about correct system preparation sequence when protonation state calculation and ligand presence are involved

Justin Lemkul jalemkul at vt.edu
Mon May 25 18:29:25 CEST 2015

On 5/24/15 1:21 PM, Gustavo Avelar Molina wrote:
> Hi everyone,
> I'm a little confused about the most correct sequence of the minimization,
> equilibration, solvatation and neutralization steps when I need to simulate
> a protein in a specific pH (through the protonation state calculation in
> this pH by using H++, for instance) and/or place a ligand in this protein (be
> it through covalent bonding or not). For instance, I've seen papers in
> which people use the following sequence: minimization, solvatation, H++
> calculation, neutralization and equilibration, which is not so intuitive to
> me. Moreover, I've noticed that the sequence affects substantially the
> resulting protonation state in H++, but not so much the pI.

H++ uses an implicit model to represent solvent, so I don't see how simply 
solvating a structure should have any effect.  The microenvironment around a 
particular residue is what dictates the protonation; it is a function of solvent 
accessibility, protein conformation, and other nearby residues.

> So, I would like to know what is the most appropriate system preparation
> sequence for a protein simulation when I need it with the protonated state
> corresponding to a certain pH and when I need to place a certain ligand in
> this protein.

I suppose it depends on the nature of the ligand, whether or not it alters the 
electrostatic properties of the microenvironment around the titratable residue(s).



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


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