AMBER Archive (2009)

Subject: Re: [AMBER] how to use amber to verify the reason for difference in affinity

From: case (case_at_biomaps.rutgers.edu)
Date: Sun Nov 29 2009 - 20:55:38 CST

On Tue, Nov 24, 2009, Josmar R. da Rocha wrote:
>
> I would appreciate if someone could give a tip or to point some
> reference on how to use amber in my problem. I tested two very similar
> compounds against a protein and one of then is 500-fold more potent than
> the other. I guess that the diference is caused mainly due to a charge
> stabilization of a deprotonate cystein through the interaction with a
> diene fragment, which is replaced by a saturated fragment in the less
> potent compound.
>
> 1-How could I verify this hypothesis?

Things more commonly work the other way around: you use computations to
generate hypotheses that are then tested experimentally.

> 2-When I use MM, is this kind of effect is taken into account?

What you describe (deprotonated cysteine, diene fragments) is well outside the
"standard" molecular mechanics model of proteins. You should plan to have to
learn a lot, and to generate your own force field components, to carry out
research on this sort of system. I don't wish to discourage you, just to
point out that what you are asking appears to be an example of a somewhat
"advanced" simulation problem.

...good luck...dac

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