Re: [AMBER] Transcription factor DNA binding - Gibbs of activation

From: Kevin Hauser <>
Date: Thu, 8 Aug 2019 07:38:03 -0700

Hi there,

On Wed, Aug 7, 2019 at 11:58 PM <> wrote:

> Dear AMBER community,
> I am a member of iGEM Thessaloniki team, an undergraduate research
> team of Aristotle University of Thessaloniki, Greece and I am sending
> you this e-mail in order to ask you some questions regarding the
> computational model of our project.
> My team and I are working on designing a DNA computer system in a cell
> free environment, based on a DNA Strand Displacement mechanism. We are
> planning on using our toolkit in order to measure the binding affinity
> of a Transcription Factor with a DNA sequence. At this point of our
> project, we are studying the binding sites of NF-κB, as a proof of
> principle.
> In an effort to create a complete model, we are trying to calculate
> the exact time that will be needed in order for the TF to bind to the
> DNA and the duration of this binding. Thus, we are thinking on
> calculating the kinetic rates of the binding reaction and that's why
> we are considering using the Eyering equation or the Collision theory.
> However, both methods need ΔG of activation for the calculations. It
> is important to be stated, that we do not have any experimental data
> concerning the binding reaction.
> Therefore, I would like to address you the following questions.
> 1) Do you think that is possible to predict the free energy of
> activation for this reaction?

In principle yes. In practice, you have 3D diffusion coupled with 2D
diffusion along the DNA (sliding across sequences and doing so with
non-digital displacement). Now that your TF is on the DNA and moving along
it, it'll undergo conformational changes when it recognizes its target
cognate sequence.

Take a look at this publication on how we approached the 2D component of
diffusion using Amber and check the references for 3D diffusion

Take a look at this publication on how Haoquan approached the kinetics of
sequence recognition using Amber:

> 2) Do you think that AMBERTools18 is suitable for our purposes?

AmberTools is probably not suitable for getting diffusion/binding kinetics
of highly charged systems in which solvent structure is important, dynamics
are key but often "slow" and you don't have a lot of experimental data. The
good news is that Amber is relatively cheap for
Academic/non-profit/government entities.

> We would really appreciate your help in the matter. Any feedback could
> be useful for our project.

If Amber is on the table for you, check out publications from Carlos
Simmerling's group, Modesto Orozco's group, and David Case's group.

> Thank you very much for your time.
> My best regards,
> Charalampos Malathounis
> _______________________________________________
> AMBER mailing list

Hope that helped,
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Received on Thu Aug 08 2019 - 08:00:03 PDT
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