Re: How to perform REMD of a system a membrane-protein system?

From: Giacomo Fiorin (giacomo.fiorin_at_gmail.com)
Date: Tue Jan 10 2017 - 10:09:04 CST

Hi Giota,

On Mon, Jan 9, 2017 at 5:34 PM, Panagiota Kyriakou <kyria008_at_umn.edu> wrote:

> Hi Giacomo,
>
> Thank you for your response and your suggestion. It is very helpful!
>
> Could you please explain to me how the hydrophobicity of the peptide
> affects the free energy barriers of the system?
>

You probably need to sample transitions between states with the peptide
adsorbed on the bilayer's surface, embedded within the bilayer, or solvated
in the water phase. Each state will be more or less stable depending on
the hydrophobic, hydrophilic, or amphiphilic character of the peptide.
(And that's not even counting the fact that the peptide will probably
change secondary structure between states).

>
> What do you think about Replica Exchange Solute Tempering (REST)? Do you
> think it could work instead of classic REMD?
> I recently read an article by Huang et al "Acceleration of Lateral
> Equilibration in Mixed Lipid Bilayers Using Replica Exchange with Solute
> Tempering <http://pubs.acs.org/doi/abs/10.1021/ct500305u>" where they
> perform REST on a bilayer with Gromacs. However, I think that a similar
> protocol can be followed with NAMD since I think there is an option for
>

It's worth a try if the bilayer is small enough, but ultimately the solute
tempering protocol will suffer from the same problems of the whole-system
tempering when you study larger bilayers. Keep in mind, however, that that
study deals with accelerating the diffusion of lipids in bilayers, for
which the intrinsic diffusion coefficient is very low due to the large
molecular size and the liquid-crystalline order of the bilayer, but the
free energy barriers are generally small (so an increase in temperature
will go a long way).

Ultimately the question is what you want to predict by these simulations.
If you don't have a good starting structure for the system, I would focus
on making a good hypothesis for that before moving forward.

Giacomo

>
> Thank you,
> Giota
>
>
>
> Panagiota Kyriakou
> Ph.D. Candidate in Chemical Engineering
> Dept. of Chemical Engineering and Materials Science
> University of Minnesota
>
>
>
> On Wed, Jan 4, 2017 at 8:24 AM, Giacomo Fiorin <giacomo.fiorin_at_gmail.com>
> wrote:
>
>> Hi Giota, it's very unlikely that you'll get decent conformational
>> sampling in the gel phase, so I would suggest sampling only temperatures
>> above the transition.
>>
>> Note also that there are probably large free energy barriers between the
>> states of the system, depending on the hydrophobicity of the peptide. Just
>> raising the temperature may not be enough to cover them, and the membrane
>> may break apart before then.
>>
>> You are probably better off running independent replicas, each prepared
>> from a different structure and compare their results.
>>
>> Giacomo
>>
>> On Tue, Jan 3, 2017 at 7:38 PM, Panagiota Kyriakou <kyria008_at_umn.edu>
>> wrote:
>>
>>> Hello NAMD community,
>>>
>>> I wish to perform an all-atom REMD simulation of a membrane-protein
>>> system (a 40-residue peptide). My membrane is a bilayer consisted of POPG
>>> and POPE lipids and I want to explore temperatures above 300K (above their
>>> gel-liquid transition temperature).
>>> Does any of you have any suggestion/advice on how to treat the lipids?
>>> Should I constrain them? Is there a maximum temperature that I should heat
>>> my system?
>>>
>>> Thank you in advance,
>>> Giota
>>>
>>> Panagiota Kyriakou
>>> PhD Candidate in Chemical Engineering
>>> Dept. of Chemical Engineering and Materials Science
>>> University of Minnesota
>>>
>>>
>>>
>>
>>
>> --
>> Giacomo Fiorin
>> Associate Professor of Research
>> Institute for Computational Molecular Science (ICMS)
>> College of Science and Technology, Temple University
>> 1925 North 12th Street (035-07), Room 704D
>> Philadelphia, PA 19122-1801
>> Phone: +1-215-204-4213 <(215)%20204-4213>
>>
>> Scholar: http://goo.gl/Q3TBQU
>> Personal: http://giacomofiorin.github.io/
>> Lab page: https://icms.cst.temple.edu/members.html
>>
>> *"As computer programmers we have a responsibility to make sure that we
>> run the computers instead of the computers running us."* - Steve
>> Oualline
>>
>>
>>
>

-- 
Giacomo Fiorin
Associate Professor of Research
Institute for Computational Molecular Science (ICMS)
College of Science and Technology, Temple University
1925 North 12th Street (035-07), Room 704D
Philadelphia, PA 19122-1801
Phone: +1-215-204-4213 <(215)%20204-4213>
Scholar: http://goo.gl/Q3TBQU
Personal: http://giacomofiorin.github.io/
Lab page: https://icms.cst.temple.edu/members.html
*"As computer programmers we have a responsibility to make sure that we run
the computers instead of the computers running us."*  - Steve Oualline

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