[gmx-users] Re: Derive the heme charge

Justin Lemkul jalemkul at vt.edu
Sat Feb 2 19:34:04 CET 2013

On 2/2/13 9:30 AM, Rui Zhang wrote:
> Dear all,
> Could anyone help me on my previous questions? Please reply me... (I know
> it might be a hard question, and I did all the works by learning myself.)
> I was very frustrated that the professor who works as the
> co-author didn't use GROMACS (and GROMOS53a6 force field), but he concerned
> about whether the heme charge is defensible before the manuscript can be
> submitted. It takes me two years to write this manuscript. I was about to
> graduate in this spring but have no paper published yet. I hope you can
> give me some clue so that I can get the manuscript at least submitted.

The best answer to the original question is that there probably is no definitive 
answer.  There are a variety of ways in which people derive parameters for 
Gromos96 force fields, but most involve empirical fitting and transferability 
between equivalent groups.  Dealing with metals and such can be quite challenging.

No one on this list is likely to give you a "peer review before peer review," if 
you will, based solely on incomplete information in an email, and it probably 
would have been better to ask questions before spending 2 years working on this 
system - what if it turns out you were wrong all along?  Why not use a force 
field that has a better-defined method for deriving partial charges?

In any case, Gromos96 53A6 does in fact have parameters for heme, though the 
charges are quite different from what you have derived.  That's not to say that 
your model isn't superior.  What you have to demonstrate is that your model 
provides some insight that can be compared to known experimental behavior. 
That's the task of any simulation model.


> On Fri, Feb 1, 2013 at 10:49 AM, Rui Zhang <rzhan001 at fiu.edu> wrote:
>> Hello,
>> I want to derive the atomic partial charges for heme in chloroperoxidase,
>> since these parameters cannot be found in the GROMOS53a6 force field.
>> Chloroperoxidase is a cysteine-ligated heme protein (high spin) much like
>> P450. In my work, I want to study the interactions between the protein
>> residues of chloroperoxidase and its substrates. Thus, I used the QM
>> software ORCA to optimize the heme-thiolate structure (TPSS/def2-SPVD), and
>> then I used CHELPG method to derive the heme charges. Could anyone tell me
>> if the method I used is suitable for my purpose?
>> In addition, the charges I obtained for Fe (0.931877) and nitrogen
>> (-0.44572, -0.34427, -0.39467, and -0.39467) are largely consistent with
>> two reference. The reference are one in 1995 (Fe: 1.0, N: -0.4; Helms et
>> al. Thermodynamics of water mediating protein-ligand interactions in
>> cytochrome P450cam: a molecular dynamics study, Biophys. J. 69: 810-24) and
>> one in recent (Fe: 0.847, N: -0.37, -0.423, -0.504, and -0.528; Favia et
>> al. (2006) Three-dimensional model of the human aromatase enzyme and
>> density functional parameterization of the iron-containing protoporphyrin
>> IX for a molecular dynamics study of heme-cysteinato cytochromes, Proteins
>> 62: 1073-84). I will greatly appreciate any comment and suggestions.
>> Best Regards,
>> Rui


Justin A. Lemkul, Ph.D.
Research Scientist
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080


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