AMBER Archive (2007)

Subject: Re: AMBER: Rate of Dissociation

From: Catein Catherine (askamber23_at_hotmail.com)
Date: Fri May 04 2007 - 21:10:02 CDT

Dear Sean,

Thank you very much for your help! May I ask you in more details regarding
the MM-PBSA approach? I used MM-PBSA approach (listed in Tutorial 3 of
amber webpage) to calculate the gibb free energy for the drug binding to the
receptor, i.e. calculate the molecular dynamics for drug-receptor complex in
their binding coordinate and use EXDI=80.0.

Regarding to the approach you suggested below to calculate the rate
constant, I could use the same approach, but I should do the molecular
dynamic calculation for the drug-receptor complex in their activated state,
and use EXDI=saturated drug condition. Did I misunderstand anything here?

Do you mind to give me some hints where and how can we find the activated
state for a dissociating complexes and EXDI for a saturated solutions?

Best regards and many thanks!

Cat

>From: Sean Rathlef <sean_at_syncitium.net>
>Reply-To: amber_at_scripps.edu
>To: amber_at_scripps.edu
>Subject: Re: AMBER: Rate of Dissociation
>Date: Fri, 04 May 2007 11:15:03 -0800
>
>We tried computing the energy barrier for association / dissociation of a
>ligand from an receptor using steered molecular dynamics simulations, thus
>taking into account the conformational changes of the protein, but this
>method proved to be computationally cumbersome and not very accurate.
>
>You should be able to compute a first order rate constant for LR --> L + R
>via MMPBSA, but you will need to reproduce the energy barrier of L-R* via
>modeling the system at infinate saturation of L. If you model at infinite
>L, then you are modeling the energy of that dissociation barrier. To do
>this via simulation using an implicit solvent, you will have to model your
>baseline LR structure (i.e., the structure of LR in water), but change the
>dielectric of your water (78.4) to that of your ligand / drug.
>
>Sean
>
>----- Original Message -----
>From: "David Mobley" <dmobley_at_gmail.com>
>To: <amber_at_scripps.edu>
>Sent: Friday, May 04, 2007 9:41 AM
>Subject: Re: AMBER: Rate of Dissociation
>
>
> > So, you ARE after the rate?
> >
> > That sounds like a hard problem. You should probably review the
> > literature on calculating protein folding rates, as what you're asking
> > is related to the question of how one would calculate a protein
> > folding rate from a simulation.
> >
> > David
> >
> > On 5/4/07, Catein Catherine <askamber23_at_hotmail.com> wrote:
> > > Dear All,
> > >
> > > Could you please kindly give me some hints if I could calculate the
>rate
>of
> > > dissociation of a drug from the receptor protein with AMBER package?
>If
> > > yes, what is the best way to do so?
> > >
> > > Best regards and many thanks!
> > >
> > > Cat
> > >
> > > _________________________________________________________________
> > > Learn English via Shopping Game, FREE!
> > >
>http://www.linguaphonenet.com/BannerTrack.asp?EMSCode=MSN06-03ETFJ-0211E
> > >
> > >
>-----------------------------------------------------------------------
> > > The AMBER Mail Reflector
> > > To post, send mail to amber_at_scripps.edu
> > > To unsubscribe, send "unsubscribe amber" to majordomo_at_scripps.edu
> > >
> > -----------------------------------------------------------------------
> > The AMBER Mail Reflector
> > To post, send mail to amber_at_scripps.edu
> > To unsubscribe, send "unsubscribe amber" to majordomo_at_scripps.edu
> >
>
>
>-----------------------------------------------------------------------
>The AMBER Mail Reflector
>To post, send mail to amber_at_scripps.edu
>To unsubscribe, send "unsubscribe amber" to majordomo_at_scripps.edu

_________________________________________________________________
Learn English via Shopping Game, FREE!
http://www.linguaphonenet.com/BannerTrack.asp?EMSCode=MSN06-03ETFJ-0211E

-----------------------------------------------------------------------
The AMBER Mail Reflector
To post, send mail to amber_at_scripps.edu
To unsubscribe, send "unsubscribe amber" to majordomo_at_scripps.edu