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

Smith, Micholas D. smithmd at ornl.gov
Tue Dec 30 17:06:08 CET 2014

In response to 4)

As Justin said, the choice of force-field is a long-standing battle in the literature; however, one thing that can be useful is to see if there exists both simulations and nmr results on a protein whose fold is similar to yours and use that as a guide. For instance, if you have NMR for a similar protein that indicates you should have a lot of helix and two MD studies were done on this similar protein and one force-field finds a lot of helix and the other finds only a modest amount it can give you an idea as to which one to use for your protein. 

Now in the absence of data like this, I would personally choose OPLS/AA, as I have used it in the past; however, using one of the more recent force-fields (Amber-99SB-ILDN or whatever the newest version of CHARMM is) would likely be just as reasonable (or some would argue better).  As for united-atom representations, I tend to stay away from unless the protein I am investigating is in the 100+ residue range, and even then if I have the resources, all-atom is still my preference.

Micholas Dean Smith, PhD.
Post-doctoral Research Associate
University of Tennessee/Oak Ridge National Laboratory
Center for Molecular Biophysics

From: gromacs.org_gmx-users-bounces at maillist.sys.kth.se <gromacs.org_gmx-users-bounces at maillist.sys.kth.se> on behalf of Justin Lemkul <jalemkul at vt.edu>
Sent: Tuesday, December 30, 2014 10:44 AM
To: gmx-users at gromacs.org
Subject: Re: [gmx-users] All-atom vs United-atom force fields and hydrogen bonds

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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