AMBER Archive (2006)

Subject: AMBER: Potential of Mean Force calculation or Steered molecular dynamics

From: a a (patd_2_at_hotmail.com)
Date: Mon Oct 09 2006 - 01:07:25 CDT

Dear Feng and Ambers,

Thank you very much for your suggestions.

Can I run Potential of Mean Force calculation (or Steered molecular
dynamics) with amber 8.0? If yes, I will try to so. If the answer is not,
could you please kindly suggest how can I do this type of calculations?

Best regards,
Ann

>From: Feng X Zhou <feng.zhou_at_abbott.com>
>Reply-To: amber_at_scripps.edu
>To: amber_at_scripps.edu
>Subject: Re: AMBER: RMSD: is it related to flexibility?
>Date: Fri, 6 Oct 2006 11:28:36 -0500
>
>Ann,
>
> Is it true the flexibility of the loop is related to the releasing
>process of the metabolite, i.e., the transition state energy is lower
>for the mutated enzyme due to a more adaptable loop to accmodate the
>distorted state when the metaboliote is coming out of the protein?
>
> This is the impression I got reading your email... and if this is
>the speculation you are working on, MD might be a right tool compared to
>DOCK since it can do dynamics ... Have you considered doing a Potential
>of Mean Force calculation (or Steered molecular dynamics) to calculate the
>binding energy & transition state energy? This way the binding
>constant and transition state barrier can both be estimated, along with a
>conformation comparison to see what exactly allowed the mutant to be more
>adaptive to distortion - that is if the MD simulation is accurate and
>realistic enough (the longer than better)
>
>Just 2 pennies -:)
>
>
>-Feng Zhou
>fzhou99_at_gmail.com
>
>
>
>
>
>
>
>
>
>
>
>
>Subject: Re: AMBER: RMSD: is it related to flexibility?
>From: Gustavo Seabra (gustavo.seabra_at_gmail.com)
>Date: Thu Oct 05 2006 - 11:08:05 CDT
>Previous message: Thomas Cheatham: "Re: AMBER: ptraj hbond analysis
>troubles"
>In reply to: a a: "Re: AMBER: RMSD: is it related to flexibility?"
>Next in thread: a a: "Re: AMBER: RMSD: is it related to flexibility?"
>Next in thread: Bill Ross: "Re: AMBER: mdcrd file"
>Reply: a a: "Re: AMBER: RMSD: is it related to flexibility?"
>Messages sorted by: [ date ] [ thread ] [ subject ] [ author ]
>
>Ann,
>If all you want is to compare flexibilities, it may be a beter idea to
>define a couple of characteristic internal distances and monitor them
>in time. For a better description of the method, take a look at:
>"Sulfide Binding Hemoglobins: Effects of Mutations on Active Site
>Flexibility"
>Fernandez-Alberti et al. Biophys. J. vol. 91, p.1698 (2006)
>Best wishes,
>Gustavo Seabra.
>On 10/5/06, a a <patd_2_at_hotmail.com> wrote:
> > Dear David,
> >
> > Thank you very much for your comments. The following is the experimental
>
> > work done previously. Both the wild type and mutated proteins form a
> > covalent complex with a drug. They both modified the drug to a
>metabolite.
> > Experimentally, we measured the metabolite concentration over the time,
> > and found mutant one produce metabolite ten times faster than the wild
>type.
> > We originally expected that it is due to different binding affinity of
>the
> > drug, but finally we found the binding affinities for these two proteins
>to
> > the drug are the same both experimentally and theoretically (docking).
>As
> > it is well documented that the rate for these protein to release the
> > metabolite is a function of a flexibility of a loop on these proteins
>(the
> > loop is mutated). Thus, we try to see if the mutation change the
> > flexibility of the loop theoretically, so as to explain the increased
>rate.
> >
> > Follow the tutorial on the web, I carried out minimization, equilibrium
>and
> > a production 1-ns MD with sander for these two proteins, and double
>checked
> > that the potential energies are stable at the production period. This is
>
> > the preliminary result that we got. The RMSD (reference to a PDB file)
>of
> > the loop of the wild type protein in average is 2.0, but 3.0 for the
>mutant
> > one. The RMSD vs time plot shown that the RMSD increase from zero and
> > reach stable (~ 4 A) at ~300 ps for the wild type and ~200 ps for the
> > mutant. Is the difference in terms of RMSD (1-2 A) and time to reach
>stable
> > (100 ps) significant enough for drawing any conclusions?
> >
> > If not, could you mind to suggest the best way to model the release rate
>of
> > metabolite B from these two proteins?
> >
> > I am new to MD calculations, just learn it several months ago from the
> > websites, your professional suggestions are valuable to me. Many thanks
>in
> > advanced.
> >
> > Best regards,
> >
> > Ann
> >
> > >From: "David A. Case" <case_at_scripps.edu>
> > >Reply-To: amber_at_scripps.edu
> > >To: amber_at_scripps.edu
> > >Subject: Re: AMBER: RMSD: is it related to flexibility?
> > >Date: Wed, 4 Oct 2006 08:08:32 -0700
> > >
> > >On Wed, Oct 04, 2006, a a wrote:
> > > >
> > > > I got two protein structures with different performance on the loop
> > > > mobilitiy, one of them move very fast, another one is about 10 time
>less
> > > > flexible, based on our experimental data.
> > >
> > >The answer probably depends on what kind of experimental data one is
> > >talking
> > >about here; that will effectively determine what is being measured and
> > >represented as "flexibility". And that, in turn, will help decide what
> > >sorts
> > >of calculations might be relevant.
> > >
> > >...regards...dac
> > >
>-----------------------------------------------------------------------

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