[gmx-users] Re: free energy calculations

[Justin A. Lemkul]

Ragothaman Yennamalli wrote:
> 
> 
> 
>     Message: 1
>     Date: Tue, 05 Jul 2011 19:14:04 -0400
>     From: "Justin A. Lemkul" <jalemkul at vt.edu <mailto:jalemkul at vt.edu>>
>     Subject: Re: [gmx-users] free energy calculations
>     To: Discussion list for GROMACS users <gmx-users at gromacs.org
>     <mailto:gmx-users at gromacs.org>>
>     Message-ID: <4E139ABC.1030107 at vt.edu <mailto:4E139ABC.1030107 at vt.edu>>
>     Content-Type: text/plain; charset=ISO-8859-1; format=flowed
> 
> 
> 
>     Ragothaman Yennamalli wrote:
>      > Hi,
>      > I want to run free energy calculations on a particular protein-ligand
>      > complex. I do not have much knowledge on this so I have some
>     questions,
>      > hopefully someone might give me clear answers.
>      > I am following the tutorial given in this link:
>      >
>     http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/free_energy/08_advanced.html
>      >
>      > My questions are as follows:
>      > 1. I am assuming that I do not need the "protein without the ligand"
>      > form for free energy calculations. Am I right?
>      >
> 
>     Free energy calculations can be done on a number of systems.  The
>     tutorial is
>     just one simple example.
> 
> 
> Thanks for the mail. So, I technically do not need both the un-complexed 
> and complexed form of the protein with the ligand.
> 

This is discussed in the tutorial:

http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/free_energy/08_advanced.html

> 
>      > 2. To use g_bar, I need to run the protein-ligand complex with
>      >     a) first with lambda ranging from 0.5 to 1 for vdw coupling and
>      >     b) followed by lambda ranging from 0.5 to 1 for coulombic
>     coupling
>      > Adding these would give the deltaG I am looking for. Am I right?
>      >
> 
>     No.  The range for lambda should be 0 to 1.  Using 0.5 to 1 gives
>     only part of
>     the free energy for the transformation, and not necessarily half.
> 
> 
> Apologies, I should have mentioned as from 0 to 1. So, the first step is 
> to do vdw coupling followed by coulombic coupling. Right?
> 

No, the opposite.  You do not want to remove vdW terms from charged species. 
This topic is addressed in the tutorial.

http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/free_energy/02_topology.html

-Justin

> 
>      > 3. Are there any papers that use g_bar function in gromacs to
>     calculate
>      > free energy?
>      >
> 
>     The g_bar tool is relatively new to Gromacs, so maybe not.  The BAR
>     method
>     itself has been around for decades though, so its applications have been
>     demonstrated in the literature many times.
> 
> 
> Thanks for pointing this.
> Raghu
> 
> 
>     -Justin
> 
>     --
>     ========================================
> 
>     Justin A. Lemkul
>     Ph.D. Candidate
>     ICTAS Doctoral Scholar
>     MILES-IGERT Trainee
>     Department of Biochemistry
>     Virginia Tech
>     Blacksburg, VA
>     jalemkul[at]vt.edu <http://vt.edu> | (540) 231-9080
>     <tel:%28540%29%20231-9080>
>     http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
> 
>     ========================================
> 
> 

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

Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
MILES-IGERT Trainee
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin

========================================