[gmx-users] All-atom vs United-atom force fields and hydrogen bonds

Justin Lemkul jalemkul at vt.edu
Tue Dec 30 16:45:41 CET 2014

On 12/30/14 9:03 AM, Jason Hill wrote:
> Hello list,
> I’m working with some allozymes that differ by only a couple of amino acids
> but that I have observed to have empirically very different binding
> affinities and thermal stabilities. I’m investigating the structural basis of
> the functional differences so I crystallized one form and am using that
> structure as the template for a molecular dynamic approach. Among results
> that I am interested in are hydrogen bonding patterns. I’ve been reading the
> primary literature for the force fields and I’m sorry to say I am still
> unclear on what I think are a couple of basic issues, ones that I hope you
> can help me figure out.
> 1) When a united-atom force field is used suck as GROMOS96 54a7 are the
> hydrogens of ALL carbons in the system subsumed into the carbon and if so are
> their position on the carbon kept track of?

Only nonpolar hydrogens are affected.  In 54A7, aromatic H are explicit, but 
anything that is CH, CH2, or CH3 is united.  There is no information about these 
H stored or tracked in any way; they simply don't exist.  The CHn atom types 
have their nonbonded parameters derived such that they include the effect of the 
attached hydrogens.

> 2) When selecting a force field is information lost in a united-atom force
> field like GROMOS96 54a7 that renders downstream analysis by tools like
> g_hbond less meaningful?

No.  Hydrogen bonding (at least within g_hbond, because atom names are 
hard-coded) involves only polar groups.

> 3) One of my favorite up to date tutorials
> (http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/lysozyme/index.html
> <http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/lysozyme/index.html>)
> uses the OPLS-AA/L force field but a lot of the literature seems to indicate
> that the newer force fields perform much better (blog review:
> http://md.chem.rug.nl/cgmartini/index.php/blog/265-comparingforcefields
> <http://md.chem.rug.nl/cgmartini/index.php/blog/265-comparingforcefields>)!
> Is the all atom parameterization so much more important than factors like
> agreement with NMR structure for down stream analysis for g_hbond or other
> things that OPLS-AA/L would still be a better choice?

The use of OPLS-AA in my tutorial is for convenience for myself; I reasoned I 
would get fewer questions like "where did all of my hydrogens go?" so I went 
with an all-atom force field.  I leave the tutorial as-is because (1) I have a 
data set that I know is highly reproducible and (2) I really don't feel like 
rewriting it.  I'm fairly sure I added a disclaimer a while back that indicated 
that users should always look into suitable force fields, rather than thinking 
the tutorial is simply a recipe of "this is how you do a protein MD simulation." 
  It's not.

> 4) For a protein in water simulation in which you were investigating the
> movement and stability of the protein, what force field would you use, and
> why?

Everyone will have their own reasons here, and this is a never-ending battle in 
the literature, depending on what metrics you're using.  I believe strongly in 
CHARMM36, because I see the results it produces every day in our group.  But 
then too, I believe in polarizable force fields over additive models, anyway :)

Most force fields will perform reasonably well for a fully folded protein. 
Gromos96 53A6 has some issues with helices, but 54A7 seems to have largely fixed 
these.  AMBER, CHARMM, and OPLS-AA variants all seem to do well, in general.



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

jalemkul at outerbanks.umaryland.edu | (410) 706-7441


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