AMBER Archive (2006)

Subject: Re: AMBER: RMSD: is it related to flexibility?

From: a a (patd_2_at_hotmail.com)
Date: Thu Oct 05 2006 - 21:50:43 CDT

Dear Gustavo,

Thank you very much for your help!

Best regards,

Ann

>From: "Gustavo Seabra" <gustavo.seabra_at_gmail.com>
>Reply-To: amber_at_scripps.edu
>To: amber_at_scripps.edu
>Subject: Re: AMBER: RMSD: is it related to flexibility?
>Date: Thu, 5 Oct 2006 12:08:05 -0400
>
>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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