As Dave, Adrian, and Thomas pointed out, you can use umbrella sampling and
combine it with WHAM to get a free energy profile for a transformation.
Here are my thoughts on free energy calculations that you can do with
AMBER:
1. If your system needs to do alchemical transformations such as change in
charge, atom type, etc, you need to use thermodynamic integration (TI).
But if there is conformational change in the alchemical transformation, TI
will not work.
2. If there is a conformational change that you want to analyze, you can
use umbrella sampling. The important thing in umbrella sampling is to find
a good reaction coordinate to mimic the transformation. In AMBER9, you can
use distance, angular, and torsional restraints for the reaction
coordinate, but in AMBER10 and 11, you can use generalized distance,
angular, and torsional restraints (such as the center of geometries of the
groups), which I think are very useful. You can also combine targetted MD
with WHAM to get a free energy surface. I think Benoit Roux as well as
Orozco's group did work on tMD/WHAM approach. All these assume that you
are interested on equilibrium dynamics.
3. The other option is to run a very long MD simulation, and analyze the
results, such as histogram analysis as Thomas pointed out. But what is a
long MD simulation? 1 ns, 1 micros, 1 millis? If you have a big system, I
do not think that this approach will work. If you have a small system such
as a monomer system, then this approach can be used to see conformational
transformations. We published a paper, which uses this methodology, to
predict the deltaG for mononucleosides, but I do not think that it will
work on bigger systems.
At the end, the computational predictions should be compared to
experimental measurements. All these calculations use force fields, which
are parameters/numbers given to the program so that you can mirror the
real nature/environment. If your system has nucleic acids in it such as
DNA/RNA/LNA or any other version, and if the property you are looking for
is something very unique, the force field might not be able predict the
experimental results. Thus, use the latest force field for your system in
doing any of the above calculations.
All the best,
Ilyas Yildirim, Ph.D.
-----------------------------------------------------------
= Department of Chemistry - 2145 Sheridan Road =
= Northwestern University - Evanston, IL 60208 =
= Ryan Hall #4035 (Nano Building) - Ph.: (847)467-4986 =
=
http://www.pas.rochester.edu/~yildirim/ =
-----------------------------------------------------------
On Thu, 24 Mar 2011, Mahmoud Soliman wrote:
>
> Dear Thomas,
> Actually your reply to Catherine has encouraged me to seek your advice about
> my case: I need to do a PMF for some reaction coordinate (nucleophilic
> attack) using QM/MM facility in Amber 10. I read through steered MD
> simulation but it sounds to me (from the comments I get from Amber
> users/developers) that SMD is a bit doggy and some people getting some
> trouble to publish work with SMD. Is there any EASY and reliable alternative
> in Amber 10 that I can apply to do a PMF for NU or PT reactions in enzyme???
> do you have any tutorial/example for the methode you explain below to
> Catherine that I can use??
> Best wishes
> Mahmoud
> On 3/24/11 5:04 PM, [1]steinbrt.rci.rutgers.edu wrote:
>
> Hi,
>
> I am not sure if this is what you mean, but if you can define a clear
> reaction coordinate x for the change you see, e.g. some distance, you can
> use ptraj to analyse the time series of movement along it, compute a
> histogram P(x) and transform it into a potential of mean force via dF=
> -RTln P(x). This is only meaningful if all points along x are well sampled
> though.
>
> Kind Regards,
>
> Thomas
>
> On Thu, March 24, 2011 10:55 am, Catein Catherine wrote:
>
> Dear Sir/Madam,
>
> I have done the MD simulations. I would like to analysis the free energy
> landscapes of a conformational change during a long MD simulations.
>
> Can I do it with ptraj or any other softwares or scripts?
>
> Best regards,
> Catherine
> _______________________________________________
> AMBER mailing list
> [2]AMBER.ambermd.org
> [3]http://lists.ambermd.org/mailman/listinfo/amber
>
>
> Dr. Thomas Steinbrecher
> formerly at the
> BioMaps Institute
> Rutgers University
> 610 Taylor Rd.
> Piscataway, NJ 08854
>
> _______________________________________________
> AMBER mailing list
> [4]AMBER.ambermd.org
> [5]http://lists.ambermd.org/mailman/listinfo/amber
>
> --
>
> *************************************************
>
> Mahmoud E. Soliman
>
> Computational Chemistry & Modeling (PhD)
>
> Department of Chemistry
>
> University of Bath
>
> Bath
>
> BA2 7AY
>
> United Kingdom
>
> [6]http://people.bath.ac.uk/mess20/
>
> [7]http://www.bath.ac.uk/person/812559
>
>
> *********************************************
>
> Mahmoud E. Soliman
>
> Lecturer of pharmaceutical organic chemistry
>
> Pharmaceutical Organic Chemistry Dept.
>
> Faculty of pharmacy
>
> Zagazig University
>
> Zagazig
>
> Egypt
>
> **********************************************
>
> Email:
>
> [8]mess20.bath.ac.uk
>
> [9]meelkot.zu.edu.eg
>
> [10]mahmoudelkot.gmail.com
>
> References
>
> 1. mailto:steinbrt.rci.rutgers.edu
> 2. mailto:AMBER.ambermd.org
> 3. http://lists.ambermd.org/mailman/listinfo/amber
> 4. mailto:AMBER.ambermd.org
> 5. http://lists.ambermd.org/mailman/listinfo/amber
> 6. http://people.bath.ac.uk/mess20/
> 7. http://www.bath.ac.uk/person/812559
> 8. mailto:mess20.bath.ac.uk
> 9. mailto:meelkot.zu.edu.eg
> 10. mailto:mahmoudelkot.gmail.com
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
>
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Received on Thu Mar 24 2011 - 09:30:03 PDT
