Mahmoud - It seems that there is no tutorial for umbrella sampling/WHAM
approach in
http://ambermd.org/tutorials , but you can check out the
following website for an example, which uses AMBER and WHAM to calculate
the PMF for butane.
http://projects.eml.org/mcm/people/wang/PMF/tutorial.html
You should also get familiar with Alan Grossfield's WHAM in order to get
the free energy surface:
http://membrane.urmc.rochester.edu/sites/default/files/wham/doc/doc.pdf
This example is for one torsional angle, but you can extend this
methodology to any case you want. The basic approach is to use NMR
restraints (distance/angle/torsion, etc.) to put bias to the potential
energy on a reaction coordinate, and then use weighted histogram analysis
to predict the PMF curve. The reaction coordinate can be anything. This
example is a 1D PMF example, and it is possible to do 2D PMF calculations
with AMBER. Note that in AMBER10/11, you can use generalized coordinates,
which I think is very useful to combine with umbrella sampling.
For the targetted MD/WHAM approach, check out the following papers. Even
though it does not use NMR restraints, the basics are the same.
Noy et al., Theoretical study of large conformational transitions in
DNA: B <-> A conformational change in water and ethanol/water, NAR 35,
3330-3338, 2007.
Banavali and Roux, Free energy landscape of A-DNA to B-DNA conversion in
aqueous solution, JACS 127, 6866-6876, 2005.
Note also that in these approaches/calculations (in the example and above
papers), you cannot have any reaction that will change the covalent
bonding of the system. Maybe you can do QMMM umbrella sampling-WHAM for
that purpose but I am not familiar with that. People in this mailing list
might comment on that.
Best regards,
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 Ilyas,
>
> Thanks so much for your email, it is actually comprehensive!
> In principle, I would like to explore the free energy profile for nucleophilic substitution reaction happens between Glu residue (Nu) and an elctrophilic carbon atom in the substrate - I start from non
> covalent intermediate and end up with a covalently bonded intermediate, so that I have to use QM/MM approach. I have had difficulty (but eventually succeeded ) to publish a proton transfer reaction for
> the same complex but using AM1/OPLS PMF/WHAM (using Dynamo software) and the main criticism I got is the AM1 level of theory. To this end, I decided to try Amber since I can use DFTB description for the
> QM part....Anyway that was my story.
>
> I think my study belongs to your second proposal (below)
>
> As I mentioned I am new to such calculations in Amber , can you forward me to some tutorial or some examples on how to set up such calculations with Amber 10? I have set up my system (Minimized and
> equilibrated), that would be appreciated!
>
> Best wishes
> Mahmoud
>
> On 3/24/11 6:25 PM, Ilyas Yildirim wrote:
>
> 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
>
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> 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
>
> http://people.bath.ac.uk/mess20/
>
> 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:
>
> mess20.bath.ac.uk
>
> meelkot.zu.edu.eg
>
> mahmoudelkot.gmail.com
>
>
>
>
>
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Received on Thu Mar 24 2011 - 12:00:02 PDT
