AMBER Archive (2009)

Subject: RE: [AMBER] binding energy of multiple ligand-receptor complex

From: 欧阳德方 (ouyangdf1978_at_hotmail.com)
Date: Fri Dec 04 2009 - 15:59:21 CST

Dear all,

    
Thanks very much for your discussion! I will try the different approaches to calculate it as your discussion.
Merry Christmas!

Regards,
Ouyang

> Date: Fri, 4 Dec 2009 15:20:58 -0500
> Subject: Re: [AMBER] binding energy of multiple ligand-receptor complex
> From: jason.swails_at_gmail.com
> To: amber_at_ambermd.org
>
> If you don't know the order of the ligand binding, then you'd probably have
> to do all permutations of the ligand binding order, like Dr. Steinbrecher
> suggested.
>
> However, I can imagine that binding order is often associated with
> conformational changes which would not be captured by MM/PBSA applied to a
> single trajectory. You may have to do multiple MD simulations with various
> ligands bound to get enough sampling of the intermediate complexes to get a
> reasonable result. MM/PBSA will only give you information about the order
> of complementary binding if the effect of the second ligand binding by the
> presence of the first ligand is purely electrostatic (or VDW).
>
> Good luck!
> -Jason
>
> On Fri, Dec 4, 2009 at 4:47 AM, <steinbrt_at_rci.rutgers.edu> wrote:
>
> > Hi all,
> >
> > >> Now I am running MD simulation for multiple ligand-receptor complex
> > >> (such as 3-4 ligand bind 1 receptor to form one complex) and want to
> > >> calculate the binding energy. If it is single ligand - single receptor
> > [...]
> > > you can do several MM-PBSA calculations then.
> > > When you have a receptor with two ligands:
> > > Define calculation1 with ligand1 and receptor1 where ligand2 is part of
> > > the receptor.
> > > Then define calculation2 with ligand2 and receptor2 where ligand1 is part
> > > of the receptor.
> >
> > Wouldnt that double-count the ligand-ligand interaction? I my opinion, you
> > would have to pick a sequence in which the ligands bind and then do MMPBSA
> > for R + L1, then R-L1 + L2, R-L1-L2 + L3 and so on. Additionally, if you
> > permute the sequence, you will get some info about (anti-)cooperativity of
> > binding and maybe an idea of the real order in which ligands bind...
> >
> > Kind regards,
> >
> > Dr. Thomas Steinbrecher
> > BioMaps Institute
> > Rutgers University
> > 610 Taylor Rd.
> > Piscataway, NJ 08854
> >
> > _______________________________________________
> > AMBER mailing list
> > AMBER_at_ambermd.org
> > http://lists.ambermd.org/mailman/listinfo/amber
> >
>
>
>
> --
> ---------------------------------------
> Jason M. Swails
> Quantum Theory Project,
> University of Florida
> Ph.D. Graduate Student
> 352-392-4032
> _______________________________________________
> AMBER mailing list
> AMBER_at_ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
                                               
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