AMBER Archive (2009)

Subject: Re: [AMBER] Single Adenine

From: FyD (fyd_at_q4md-forcefieldtools.org)
Date: Thu Aug 27 2009 - 16:20:48 CDT

Ros,

> Thank you very much for your answer! Actually, the interaction I am trying
> to study is with an anti-cancer drug that has a Cu(II) atom. The metal is
> coordinated with 2 glycinate molecules. We have X ray data of the
> interaction between adenine and this copper-complex.

ok I understand better your molecular system now. Indeed, an isolated
adenine-CuII complex was quite strange ;-)

> I am trying to
> reproduce this experiment using MD, so, the adenine with the drug will
> interact non-covalently.
>
> What do you think?

I would say try & see. Get the charges for your 2 glycinates-Cu2+
complex with 4 covalent bonds without adenine and see how a nearby
adenine would interact with Cu2+ in this system during MD. Then, you
could try to modify the topology/ligands of your complex if the 1st MD
simulations are not satisfying. For sure, the charge of Cu2+ will be
important here...

regards, Francois

> 2009/8/27 FyD <fyd_at_q4md-forcefieldtools.org>
>
>> Dear Ros,
>>
>> Thanks for the help! I have a single adenine working with parm and top
>>> files
>>> made from tleap.
>>>
>>> Quick question, what is the best way to add two molecules so they can
>>> interact?
>>> 1- Make a pdb with both molecules and then do all the fiddling of external
>>> parameters in tleap
>>> 2- Join somehow directly on tleap once each molecule has its external
>>> parameters loaded
>>>
>>
>> Let's take two different examples:
>>
>> -1) a polyanion such as an oligonucleotide neutralized by Na+ ions in a box
>> of explicite water molecules: here, each Na+ ion is not covalently connected
>> to a phosphate group. Na+ are present to neutralize the system and are free
>> to interact with phosphate groups, with any other chemical groups and/or to
>> be solvated.
>>
>> -2) a metal complex such as heme with iron or your adenine-Cu2+ complex.
>> You have two options here:
>>
>> (a) You decide to make your adenine-Cu2+ complex not covalently connected
>> and the total charge of adenine and Cu2+ will be 0 and +2, respectively. In
>> this case, you can take the force field (FF) library for adenine from the
>> Amber FF topology database and create a FF library for Cu2+ (as for Na+).
>>
>> (b) You decide to make a covalent bond between adenine & Cu2+, the total
>> charge of Cu2+ will strongly decrease and you will have to build a new FF
>> library for this adenine-Cu2+ complex. Antechamber does not handle metal
>> complexes. You can use R.E.D. http://q4md-forcefieldtools.org/RED/ or
>> R.E.D. Server http://q4md-forcefieldtools.org/REDS/ for that. In this
>> case, you have to carefully check that a connectivity between adenine and
>> the metal is present (if not added by Ante_R.E.D., add it manually) in the
>> P2N input file. See our tutorials @
>> http://q4md-forcefieldtools.org/Tutorial/. As you have a physical bond
>> between adenine & Cu2+, both components of your molecular system will
>> obviously remain connected during MD simulations.
>>
>> regards, Francois

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