[gmx-users] More suitable force field and water model

Fri Jun 20 14:30:27 CEST 2014

On 6/20/14, 3:36 AM, Mohsen Ramezanpour wrote:
> Hi Mark,
>
> You are right.  :-)
>
> regarding quantities I mentioned (e.g, free energies and active site
> structure properties):
> How if we simulate our system twice? once using Gromos 53a6 and its
> parametrized water model (SPC, I guess) to estimate free energies and the
> second time using another force field which will not result in instability!
> In this way we can ensure our results are more precise. Of course it will
> cost more time.
>
> Please let me know your point of view about it.
>

Well, if you calculate a binding free energy to a structure that may not be 
sufficiently stable or may sample nonphysical structures, then the binding free 
energy will probably be wrong.  The 54a7 parameter set improved helical 
stability and is based on the same principles as 53a6, so I would say just move 
on from 53a6.

-Justin

>
>
> On Thu, Jun 19, 2014 at 8:59 PM, Mark Abraham <mark.j.abraham at gmail.com>
> wrote:
>
>> Hi,
>>
>> It would be miraculous if there was a good solution for all observables. A
>> rigid, symmetric 3-point water molecule without VDW parameters on the the
>> hydrogen atoms has 2 spatial, 2 charge, and 2 VDW parameters. That's not
>> much freedom, and most of the 6-parameter space is obviously wrong, too.
>> All you can do is pick a model that does something right (e.g. was the one
>> used to parameterize the force field), accept that your model physics is a
>> model, and remain alert for known and new problems. Even the quantum
>> chemists argue about how to model small clusters of water! ;-)
>>
>> Mark
>>
>>
>>
>> On Thu, Jun 19, 2014 at 3:55 PM, Mohsen Ramezanpour <
>> ramezanpour.mohsen at gmail.com> wrote:
>>
>>> Dear Justin,
>>>
>>> On Thu, Jun 19, 2014 at 3:11 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>>>
>>>>
>>>>
>>>> On 6/19/14, 5:59 AM, Mohsen Ramezanpour wrote:
>>>>
>>>>> Dear Gromacs Users,
>>>>>
>>>>> I have read some articles about the more appropriate combination of
>>> force
>>>>> field and water model for different simulations of interest.
>>>>> It is confusing and too difficult to decide which combination is the
>>> best
>>>>> one. Besides according to articles I read, I am in doubt now and not
>>> sure
>>>>> which combination should I choose.
>>>>>
>>>>>
>>>> This is actually very straightforward.  Every force field was
>>> parametrized
>>>> using a certain water model.  That's the one you use unless there is
>>> clear
>>>> evidence that a different model works better for some reason.  There
>> are
>>>> very few deviations from the original parametrizations of which I am
>>> aware,
>>>> and most improvements are only small.
>>>>
>>>>
>>>
>>>
>>>>
>>>>   As I understood, the SPC and TIP4P are recommended for biomolecular
>>>>> simulations and some authors have also recommended SPC.
>>>>>
>>>>>
>>>> Without context, there's not much value to that statement.  On their
>> own,
>>>> some water models reproduce certain bulk properties better than others,
>>> but
>>>> no water model is perfect.  If you were to combine TIP4P with Gromos or
>>>> something, I'd say that's probably unsound, even if TIP4P is "better"
>> in
>>>> terms of whatever you've chosen to look at.
>>>>
>>>> Yes,
>>> Please have a look at the abstract (
>>> http://www.ncbi.nlm.nih.gov/pubmed/16178604)
>>> and also the conclusion of (
>>> http://scitation.aip.org/content/aip/journal/jcp/108/24/10.1063/1.476482
>> )
>>> What do you mean exactly by "something"? do you mean TIP4P does not
>> behave
>>> good enough in combination with other force fields too?!
>>>
>>>>
>>>>   Although SPC/E seems the best one in non-polarizable models for bulk
>>>>> properties of water but for different quantities of interest such as
>>>>> hydration free energy, hydration enthalpy, entropy, heat capacities
>> etc.
>>>>> some special combinations will be more appropriate.
>>>>>
>>>>> I found that although using a FF+water model will result in a precise
>>>>> enough quantity but we can not rely on some other quantities of our
>>>>> simulation!
>>>>> By this I mean, If we are interested in hydration free energy, the
>> best
>>>>> option seems to be Gromos 53a6 and SPC or SPC/E model. But if we are
>>>>> interested in other quantities as well, other combinations will be
>>>>> preferred.
>>>>>
>>>>>
>>>> That's not necessarily true; I've seen demonstrations of other
>>>> combinations yielding very good hydration free energies.
>>>
>>> You are right, but some of them give more precise results and work for
>> most
>>> cases! The conclusion of (
>>> http://scitation.aip.org/content/aip/journal/jcp/108/24/10.1063/1.476482
>> )
>>>
>>>>
>>>
>>>>
>>>>> In fact I am interested in Protein-ligand binding free energy and also
>>> its
>>>>> Enthalpy and Entropy contributions as well.
>>>>> I guess in this case it is better to choose Gromos+SPC or SPC/E. But I
>>> am
>>>>> not sure.
>>>>>
>>>>>
>>>> If you're using Gromos96 53a6, it is known to produce helical
>>> instability.
>>>>   So the hydration free energies may be good, but the structure of the
>>>> protein may suffer from artifacts.
>>>
>>>
>>>
>>> Yes, I want to use this ff because of our main quantities of interest.
>> But
>>> we also are interested in other quantities (for example our active site
>>> structure which is composed of helices, its flexibility, etc). the main
>>> problem I mentioned was:
>>> How can we rely on other quantities from our simulation while we have
>>> chosen some special combinations?
>>> No body has investigated all quantities of simulation for all ff and
>> water
>>> models combinations, what can be the solution?
>>>
>>>
>>>>
>>>>
>>>>   I think it is also related to properties of our system components
>>> (charge,
>>>>> etc.). for example for sugars or lipids.
>>>>>
>>>>> Is there any article which has compared these in details? Please let
>> me
>>>>> know.
>>>>>
>>>>
>>>> dx.doi.org/10.1021/jp0641029
>>>
>>>
>>> Some of my comments was from the same article! please have a look at the
>>> abstract and conclusion
>>>
>>>>
>>>> Thanks in advance
>>>> -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
>>>>
>>>> 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 601
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalemkul at outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

==================================================