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[Justin A. Lemkul]

mohsen ramezanpour wrote:
> Dear Dr.Justin
> 
> I remember I had read this toturial.
> I asked in gmx.groups which method can I select if I want to evaluate 
> binding free energy?
> And the answer was Umbrella Sampling!
> 

And your reply was that you can't do umbrella sampling efficiently.  So the 
natural conclusions is you have to look for alternate methods.

> Besides,
> You recommended using free energy cycles in this gmail
> I just wanted to know other toturials.
> Please let me know if there are any other

If it's not posted on the Gromacs website and you can't find another by 
searching the web, probably one doesn't exist.  If no one has invested the time 
to make your life easier, you'll have to do things that a tutorial author would 
otherwise have to do for you: read the manual, read lots of literature, and 
define a small test case with a well-defined answer (maybe one that's already 
published) to validate your procedure.

-Justin

> Thanks in advance for your reply
> 
> 
> On Sun, Feb 13, 2011 at 3:55 PM, Justin A. Lemkul <jalemkul at vt.edu 
> <mailto:jalemkul at vt.edu>> wrote:
> 
> 
> 
>     mohsen ramezanpour wrote:
> 
>         Dear Dr.Justin
> 
>         I couldn't find any tutorial for doing free energy cycles with
>         gromacs.
>         Then I was forced to select Umbrella sampling,I read your
>         toturial and it was very useful for me.I know it approximately
>         good now.
>         Please let me know if there are any tutorial for free energy cycles.
>         I want to learn how I can do this.
> 
> 
>     When asking if there are tutorials, you should first check the
>     Tutorials page; that's why it exists:
> 
>     http://www.gromacs.org/Documentation/Tutorials#Free_Energy_Calculations
> 
>     That said, both of those tutorials are out of date, relying on very
>     old Gromacs versions.  The fundamental principles still stand,
>     though.  Read in the manual about new .mdp options and new methods
>     for calculating free energy.
> 
>     -Justin
> 
>         Thanks in advance for your guidance
>          
>         On Sat, Feb 12, 2011 at 4:50 PM, Justin A. Lemkul
>         <jalemkul at vt.edu <mailto:jalemkul at vt.edu>
>         <mailto:jalemkul at vt.edu <mailto:jalemkul at vt.edu>>> wrote:
> 
> 
> 
>            mohsen ramezanpour wrote:
> 
>                Dear All
> 
>                I want to evaluate the binding free energy of protein-dryg.
> 
>                My protein has so many atoms(5000 atoms),it make running
>         too long.
>                I want to use Umbrella sampling for this.
> 
>                Can I separate active site of protein (a radious of 3 nm
>         around
>                of my drug )and do my work on this system?
> 
> 
>            I would think that such a fractured system would suffer from a
>            number of unpredictable artifacts.  Protein structure is fairly
>            sensitive, so you'd have to apply lots of artificial
>         restraints to
>            preserve geometry, but then what if even small conformational
>            changes are needed to for the protein to properly bind the drug?
> 
>            Umbrella sampling is one of the more laborious ways of
>         calculating
>            binding energies.  Free energy cycles would probably be
>            significantly more efficient, since you can use a smaller box
>         size
>            and (in all likelihood) run shorter simulations that still
>         converge.
> 
>            -Justin
> 
> 
>                Thanks in advance for your guidances.
>                Mohsen
> 
> 
>            --     ========================================
> 
>            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> <http://vt.edu> | (540)
>         231-9080
> 
>            http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
> 
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> 
> 
>     -- 
>     ========================================
> 
>     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
>     http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
> 
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> 

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

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

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