Dear Ilyas,
Thanks a lot,
Yes the molecules get appart during the simulation no matter the size os the box, the bigger the quicker they fall appart. So I like your idea of using constraints.
I am trying to study the interaction of two drug molecules for HIV, no proteins involved at this moment. I would like to get information about their mutual interactions, energies, type of interactions, preferences, whatever than can teach me something about their preferences and interactions.
So I like your idea of using restraints but I would like to ask you several questions with your permission:
1) what force constant would you reccomend to use for the constraints?
2) what initial distance between the two molecules would you reccomend to use?
3) until now i tried 20ns dinamics should I use more to make an effective search of the space for the interactions of two drugs?
4) would be possible somehow to estimate the energy of interaction between the two molecules during or after the simulation?
5) Or clustering the most common forms of interaction after the dynamics, for that how long would you reccomend to perform it?
Thanks a lot!
Any additional suggestion will be highly appreciated,
Thanks a lot,
Fabian
On Apr 24, 2014, at 4:12 PM, Ilyas Yildirim <i-yildirim.northwestern.edu> wrote:
> 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.
> -----------------------------------------------------------
> = Department of Chemistry - 2145 Sheridan Road =
> = Northwestern University - Evanston, IL 60208 =
> = Ryan Hall #4035 (Nano Building) - Ph.: (847)467-4986 =
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> = http://www.linkedin.com/in/yildirimilyas =
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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
>>
>>
>> _______________________________________________
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>> http://lists.ambermd.org/mailman/listinfo/amber
>>
>
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> 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
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Received on Sun Apr 27 2014 - 22:30:02 PDT
