[gmx-users] Binding energy of membrane protein to the membrane lipids

[sojovictor]

Thanks so much, Justin!

Your comments and paper are very helpful indeed. With "by eye" I meant I
just need to know whether one is bigger than the other, but you're complete
right: no need to speak in qualitative terms when I can quantitatively
determine DeltaDeltaG.

Thanks again!


Victor Sojo




On 23 February 2014 17:37, Justin Lemkul [via GROMACS] <
ml-node+s5086n5014747h97 at n6.nabble.com> wrote:

>
>
> On 2/23/14, 11:54 AM, sojovictor wrote:
>
> > Thanks, Justin! That's really helpful indeed.
> >
> > You are correct, I want to know what's the energy change in replacing
> one
> > lipid with the other, hypothesising that going to the "wrong" lipid will
> > imply an energetic cost.
> >
> > Via umbrella sampling, I would thus:
> >
> > 1) Set up a full system with protein, lipids, solvent, and ions.
> > 2) Pull the protein perpendicularly out of the membrane and into the
> solvent
> > (which means I'd need a lot of solvent in the direction of the pull,
> such
> > that there's always enough space to fit the protein and still avoid
> boundary
> > interactions, as you explain in you tutorial, thanks!).
> > 3) Do the exact same thing with the other system, independently.
> > 4) See just by eye what the difference is and hope it matches my
> prediction.
> >
>
> I don't understand what "by eye" means here.  You'll get a free energy
> difference between the embedded and solvated states, i.e. the
> binding/insertion
> energy.  There's nothing qualitative about that.  That's deltaG for a
> particular
> lipid type, and the deltadeltaG is simply the difference between the two.
>
> > Now, my question about using umbrella sampling for this purpose: is it
> > reasonable to use the whole membrane (say, the group of lipids) as my
> > immobile reference? In your tutorial you use a chain, in which all
> members
> > are covalently bound to each other, so I didn't know whether you could
> use a
> > group of independent molecules instead. I assume it will be fine, then.
> >
>
> Don't assume from the tutorial that you need an immobile reference.  The
> fact
> is, you don't.  You need to define a sensible reaction coordinate that
> describes
> embedded and water-solvated states.  Neither of those intrinsically
> requires any
> sort of position restraint.
>
> What I had was a very specific case, and if you read my paper from which
> the
> tutorial was derived, you will find that the restraints there are used for
> a
> special purpose to mimic fibril stability.  That's not the case in most
> umbrella
> sampling runs.  During the generation of configurations, you may need some
> restraints to prevent perturbation of the bilayer structure, but that
> depends on
> how you generate those configurations.  A more pertinent example would be
> http://dx.doi.org/10.1021/jp202217f.
>
> -Justin
>
> --
> ==================================================
>
> Justin A. Lemkul, Ph.D.
> Ruth L. Kirschstein NRSA Postdoctoral Fellow
>
> Department of Pharmaceutical Sciences
> School of Pharmacy
> Health Sciences Facility II, Room 601
> University of Maryland, Baltimore
> 20 Penn St.
> Baltimore, MD 21201
>
> [hidden email] <http://user/SendEmail.jtp?type=node&node=5014747&i=0> | (410)
> 706-7441
> http://mackerell.umaryland.edu/~jalemkul
>
> ==================================================
> --
> Gromacs Users mailing list
>
> * Please search the archive at
> http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before
> posting!
>
> * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
>
> * For (un)subscribe requests visit
> https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or
> send a mail to [hidden email]<http://user/SendEmail.jtp?type=node&node=5014747&i=1>.
>
>
>
> ------------------------------
>  If you reply to this email, your message will be added to the discussion
> below:
>
> http://gromacs.5086.x6.nabble.com/Binding-energy-of-membrane-protein-to-the-membrane-lipids-tp5014735p5014747.html
>  To unsubscribe from Binding energy of membrane protein to the membrane
> lipids, click here<http://gromacs.5086.x6.nabble.com/template/NamlServlet.jtp?macro=unsubscribe_by_code&node=5014735&code=c29qb3ZpY3RvckBnbWFpbC5jb218NTAxNDczNXwtNzcxNzkxOTc=>
> .
> NAML<http://gromacs.5086.x6.nabble.com/template/NamlServlet.jtp?macro=macro_viewer&id=instant_html%21nabble%3Aemail.naml&base=nabble.naml.namespaces.BasicNamespace-nabble.view.web.template.NabbleNamespace-nabble.view.web.template.NodeNamespace&breadcrumbs=notify_subscribers%21nabble%3Aemail.naml-instant_emails%21nabble%3Aemail.naml-send_instant_email%21nabble%3Aemail.naml>
>


--
View this message in context: http://gromacs.5086.x6.nabble.com/Binding-energy-of-membrane-protein-to-the-membrane-lipids-tp5014735p5014766.html
Sent from the GROMACS Users Forum mailing list archive at Nabble.com.