[gmx-users] How to examine our created topology

[Justin Lemkul]

On 2/20/15 8:14 AM, Faezeh Pousaneh wrote:
> Dear Justin
>
> I have had asked you a question recently ''[gmx-users] How to examine our
> created topology
> <https://www.mail-archive.com/gromacs.org_gmx-users@maillist.sys.kth.se/msg09758.html>''.
> and you helped me with giving ABT structure of the molecule I am studding,
> lutiidne.
>
>   late reply, but I was checking the given topology in ATB. I am afraid it
> does not produce expected behavior in water solution. One for example; it
> is known that they mix at room temperature, but the given structure demix.

This suggests the hydration free energy is wrong.

> That is the problem I also have in my own created topology. It is difficult
> for me to get agreement with experiment for bulk lutidine, and its aqueous
> solution at the same time.
>
> Following this point, I would like to ask a general question ;
> In order to study a binary mixture, for example lutidine and water here,
> should I choose the charge distribution of lutidine (which I get from
> quantum chemistry) from lutidine surrounded by lutidine, or lutidine
> surrounded by water? that makes difference result in properties of bulk
> lutidne and water lutidine mixture.
>

The practical problem with the Gromos force fields is their empirical nature. 
The relationship to QM (unlike force fields like AMBER and CHARMM) is loose, at 
best.  Empirical fitting is done against condensed phase observables - density 
of neat liquid, the structure of that liquid, hydration free energy in various 
solvents, etc.  Obtaining those experimental data for targeting can be 
challenging, but that's what you need to use.  You can get an initial guess of 
the charge distribution from QM, but you won't necessarily wind up with anything 
like that when the parametrization is done.  Given that Gromos force fields are 
UA, there's little room for adjusting charges; most carbon groups have fixed 
properties (e.g. zero charge for alkyl substituents, etc) so you lose some 
flexibility.

It may be wiser to simply use a different force field if the present choice 
doesn't work or requires too much effort.

-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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