[gmx-users] using SPC water with Charmm FF

Tue Dec 8 15:22:10 CET 2015

I agree, Justin, that the gold-standard would be to compare SPC derived values to TIP3P in a very systematic way; however, it isn't just pure-water, small peptides, and disordered peptides that show that SPC can be used with Charmm. Indeed a recent binding study (Effects of water models on binding affinity: evidence from all-atom simulation of binding of Tamiflu to A/H5N1 neuraminidase. From Scientific World Journal (2014), 536084/1-536084/15, 15 pp) demonstrates that the SPC actually performs better than TIP3P for the Wild-Type neuraminidase (though binding to mutations is slightly better with TIP3P). 

Further large scale testing of Charmm with non-TIP3P water has been done (see: Molecular Dynamics Simulations of Proteins: Can the Explicit Water Model Be Varied? DOI: 10.1021/ct700053u ). If anything the validity of SPC with Charmm is system dependent and if one runs a simulation with Charmm+SPC/E, it is important to seek out direct comparisons between experimental work and your simulation for validation purposes.

What I am trying to get across is that the large simulation may not be a complete waste; it needs to be treated carefully and it should be made explicit in any manuscript produced using the simulation that SPC/E was used along with justification as to what differences you may expect to see if performed in TIP3P instead (ideally it would also include a short test MD with TIP3P for the system to demonstrate that the differences will be by and large quantiative and not qualitative).

===================
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 08, 2015 8:37 AM
To: gmx-users at gromacs.org
Subject: Re: [gmx-users] using SPC water with Charmm FF

On 12/8/15 8:32 AM, Smith, Micholas D. wrote:
> I would mildly disagree with Justin on this one. Although Charmm should
> ideally be used with TIP3P (as Justin noted being one of the force-field
> developers and all), there have been a number of papers that show that SPC/E
> is not entirely incorrect (see below). What you would need to do is see if
> there is any experimental evidence you can compare to as a sanity check;
> though, many of the papers I cite below do indicate that SPC/E does still get
> the overall dynamics correct even when used with Charmm.
>
> --------------------------------- Citations of interest.
>
> Force-Field Induced Bias in the Structure of Aβ21-30: A Comparison of OPLS,
> AMBER, CHARMM, and GROMOS Force-Fields. DOI: 10.1021/acs.jcim.5b00308
>
> Structure of Aqueous Proline via Parallel Tempering Molecular Dynamics and
> Neutron Diffraction. DOI: 10.1021/jp0714973
>
> Testing the inter-operability of the CHARMM and SPC/Fw force fields for
> conformational sampling. DOI: 10.1080/08927022.2013.824574  (note* this is an
> SPC/E derivative water model, you milage may vary)
>
> Local Order, Energy, and Mobility of Water Molecules in the Hydration Shell
> of Small Peptides. DOI: 10.1021/jp909090u
>
> Free Energy Landscapes of Alanine Oligopeptides in Rigid-Body and Hybrid
> Water Models. DOI: 10.1021/acs.jpcb.5b02937
>

The tests that need to be done would involve whether or not the combination of
CHARMM + SPC (or SPC/E) reproduce the QM target data of the force field (in
vacuo water interactions) and condensed-phase behavior (e.g. free energies of
solvation).  Maybe that exists, but absent that demonstration, my stance remains
(and that of my PI, who I quote as saying "it's totally wrong to use CHARMM with
SPC").  Using very complex systems like disordered proteins and tempered MD is
not a very strong justification to me.  You might get some overarching
properties more or less correct, but I am very skeptical.  As someone who does
force field development, never underestimate the subtle effects of a small
inaccuracy even in a large system.

-Justin

> -Micholas
>
> ________________________________________ 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: Monday, December 07, 2015 8:14 PM To:
> gmx-users at gromacs.org Subject: Re: [gmx-users] using SPC water with Charmm
> FF
>
> On 12/7/15 6:59 PM, jhon espinosa wrote:
>> Hi allI finished running the 50 ns MD Simulation of a very large system (17
>> Million atoms).It is a capsid in water. I used charmm FF for the protein
>> and spc for the water.I am studying temperature triggered structural
>> transitions.Since Charmm FF is build based on TIP3p water model, are my
>> simulation results wrong?Is there any main issue that I should
>> know?ThanksJohn
>>
>
> Sorry to say that is an invalid physical model.  The balance of forces will
> be totally wrong.
>
> -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
>
> jalemkul at outerbanks.umaryland.edu | (410) 706-7441
> http://mackerell.umaryland.edu/~jalemkul
>
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--
==================================================

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
http://mackerell.umaryland.edu/~jalemkul

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