[gmx-users] Determining a ligands permeability

[Du, Yu]

Hi, Justin, 

Thanks for your question. Presume that ligands were in only one side of the box outside of the membrane. 

1)In metadynamics, the membrane will be pushed by the ligands. After long time simulation, the membrane may move along the Z-axis.

2)In steer MD, one ligand will be pulled across the membrane and the membrane can also moves along the Z-axis.

This is the reason that I said some POSRES should be applied on the Z-axis of the lipids.

So, what is your opinion, Justin?

Regards, 
Yu


> -----Original Messages-----
> From: "Justin Lemkul" <jalemkul at vt.edu>
> Sent Time: 2017-11-06 01:14:22 (Monday)
> To: gmx-users at gromacs.org
> Cc: 
> Subject: Re: [gmx-users] Determining a ligands permeability
> 
> 
> 
> On 11/5/17 7:40 AM, Du, Yu wrote:
> > Hi,
> >
> > I don't study the membrane permeability of small molecules and can't give related papers.
> >
> > All in all, you need to first successfully simulate the lipid-small molecule system and then enhanced sampling because of the time scale of ligand diffusing across the membrane.
> >
> > There are some approaches to study it, such as, Metadynamics and steer MD.
> >
> > For Metadynamics, you can use the PLUMED with GMX and exercise larger confining potential if the ligand further away from the membrane in the water. Then, compare the chance or time that one ligand can penetrate across the entire or in the half of membrane. You can add excessive ligands in the water.
> >
> > For steer MD, you can follow Justin's tutorial. In both approaches, lipids should be under some position restraints.
> 
> Why would the lipids need to be restrained in this case? I would argue 
> the opposite. It's a spurious force in this case.
> 
> -Justin
> 
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> Justin A. Lemkul, Ph.D.
> Assistant Professor
> Virginia Tech Department of Biochemistry
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