On 6/19/16 11:03 AM, Alexander Alexander wrote:
Hello Mark, I still need help choosing the right method of neutralization of my system. I am wondering how the final states of the surface-binding process can shed light on choosing the feasible method of neutralization, here, either protonation (deprotonation) of amino acid and peptide or adding ions Na+ (Cl-)?
In the generic "charge neutralization" discussions here in recent days, people are talking about artifacts associated with using non-neutral simulation systems and relying on a uniform background charge from PME to "neutralize" these systems. In some cases, the artifacts can be quite pronounced so counterions are a simple fix.
Neutralizing side chains has important physical consequences; you should choose the protonation state based on the actual physical properties of the system and the chemical environment (e.g. solution, the calculate pKa values of the species, etc). Simply neutralizing side chains to fit a preconceived notion that the solute should be neutral (conflating the PME issues with real physical issues) is a dangerous road to go down.
For example, in one sample, I neutralized the Glutamic(zwitterionic form) by protonating it and then in simulation, it gradually absorbed firstly to the surface via one of the Hydrogen(C-H) in the end of the side chain, and then laid steady down while NH3 group was pointing up. In another sample, again I neutralized the Arginine(zwitterionic form) by deprotonating it and then in simulation, it absorbed firstly to the surface via the COO(-) group in the backbone, and then laid steady down similar to the Glutamic.
Welcome to the challenge of using fixed charge/fixed topology simulations. Protonation states, in real systems, can vary. Using traditional MD, they cannot. There are methods to get around this (e.g. constant-pH simulations, but those are not - to my knowledge - readily available in GROMACS, though people have published wrapper-type approaches to doing this).
What you need to simulate is the most probable form of your peptides under whatever the solution condition is. Deprotonating Arg requires crazily basic conditions, which may or may not be relevant to what you're studying. Perhaps the protonation state does vary during the binding mechanism. That's a challenge for you to address based on your knowledge of your specific system and published studies of similar systems.
-Justin -- ================================================== Justin A. Lemkul, Ph.D. Ruth L. Kirschstein NRSA Postdoctoral Fellow Department of Pharmaceutical Sciences School of Pharmacy Health Sciences Facility II, Room 629 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.
