If the two molecules will fall apart, you need to set a distance
restraint between them such that they will be pushed to stay in contact
during the MD. It is not clear what the system you are trying to study is.
If it does not include any protein or nucleic acid structures in it (and
only two small molecules) I would say you can use implicit solvent model
combined with distance restraints. This will be much faster. Basically you
need to get an ensemble of structures for the interaction of the two
molecules. Explicit solvents might not sample the phase space enough.
Again, if you have protein or nucleic acid in the system, this method
requires more complex restraints in the system (such that the protein or
nucleic acid structure won't fall apart in the implicit solvent
simulation).
Ilyas Yildirim, Ph.D.
-----------------------------------------------------------
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= Northwestern University - Evanston, IL 60208 =
= Ryan Hall #4035 (Nano Building) - Ph.: (847)467-4986 =
= Website : http://ilyasyildirim.wordpress.com =
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On Thu, 24 Apr 2014, Fabian Glaser wrote:
> Dear David,
>
> Thanks a lot, no they are not known to form dimers, they form crystals of course but I thought I could learn something about their different interactions or similar using amber. And you are right about they getting apart during the simulation.
>
> They form crystals of course, but I wanted to be able to say something about their "differences" or similarities in forming the crystals or at least about their interactions in solution, as a way to propose experiments or improve the way they are given to the patients (currently two different crystals).
>
> One of their main problems of course is solubility, so I am really firing in the dark for the moment.....
>
> Any suggestion would be great.
>
> Thasnks a lot,
>
> Fabian
>
>
> On Apr 24, 2014, at 3:07 PM, David A Case <case.biomaps.rutgers.edu> wrote:
>
>> On Thu, Apr 24, 2014, Fabian Glaser wrote:
>>>
>>> I am interested to calculate the free energy of interaction on many
>>> frames of MD for two drug like molecules, I plan the following:
>>>
>>> 1) Prepare the molecules with antechamber
>>> 2) Run MD in vacuum or water
>>> 3) Calculate MM-PBSA as you did for a protein-ligand on
>>> http://ambermd.org/tutorials/advanced/tutorial3/
>>
>>>
>>> Is that a good idea for two copies of drug molecules (e.g. RITONAVIR)?
>>
>> In principle, it doesn't matter what the "ligand" and "receptor" are: they
>> could both be drug molecules. But is seems likely that the two drug molecules
>> may move apart from each other during the MD simulation, which will lead
>> to a very small free energy of interaction. But perhaps the molecule is
>> known to dimerize(?)
>>
>> ....dac
>>
>>
>> _______________________________________________
>> AMBER mailing list
>> AMBER.ambermd.org
>> http://lists.ambermd.org/mailman/listinfo/amber
>
>
>
> _______________________________
> Fabian Glaser, PhD
>
> Head of the Structural Bioinformatics section
> Bioinformatics Knowledge Unit - BKU
>
> The Lorry I. Lokey Interdisciplinary
> Center for Life Sciences and Engineering
> Technion - Israel Institute of Technology
> Haifa 32000, ISRAEL
>
> fglaser.technion.ac.il
> Tel: +972 4 8293701
> Fax: +972 4 8225153
>
>
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
>
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Received on Thu Apr 24 2014 - 06:30:02 PDT
