Re: [AMBER] Chirality of amines in GAFF

From: Dean Cuebas <>
Date: Wed, 14 Apr 2010 17:12:51 -0500

> From: FyD <>
> Reply-To: AMBER Mailing List <>
> Date: Wed, 14 Apr 2010 14:51:52 -0500
> To: AMBER Mailing List <>
> Subject: Re: [AMBER] Chirality of amines in GAFF
> Dear Dmitry Nilov,
>> Amines of the type NHRR' are chiral because of the lone pair of electrons.
>> The energy barrier for inversion of stereocenter is about 7 klcal/mol.
>> I wonder if there is some mechanism in GAFF to prevent the amine
>> inversion. I suppose that 7 klcal/mol barrier crossing is a low-probability
>> event on the time scale of MD simulations, nevertheless I've observed
>> inversion of my amine during equilibration stage.

I find it interesting that your protonated amine is inverting at all, since
protonated amines cannot invert. In the real world, the inversion of chiral
amines is strictly pH dependent, with inversion rates increasing with
increasing pH, because the rate determining step is deprotonation (because
only neutral amines can invert), followed by rapid inversion.

At pH 7, deprotonation rates of tertiary amines are about once every 10
microseconds, then very rapid inversions at a rate of once every 1-10 nsec,
until protonation occurs again.

In a nutshell, once a NHRR' "stereoisomer" has been picked, it's stuck that
way for up to 10 microseconds (at least at physiological pH).

Is it normal for the MD code to allow protonated tertiary amines to
invert??? The bottom line is that it shouldn't.

my 2cent,


> I am not sure you are right when you say that a tertiary amine NHRR'
> is chiral. I think the nitrogen of such a tertiary amine NHRR' is NOT
> asymmetric. I even wonder if this interconversion is not normal: The
> only question is how OFTEN during MD simulations this should be
> observed. On the contrary, quaternary ammoniums (+)NHRR'R" do have an
> asymmetric nitrogen & present an optical activity.
> Just my personal opinion...
> Please, see (which is ambiguous)
> & better
> & then
> regards, Francois
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Received on Wed Apr 14 2010 - 15:30:04 PDT
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