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 jalem...@outerbanks.umaryland.edu | (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 gmx-users-requ...@gromacs.org.
