AMBER Archive (2009)

Subject: Re: [AMBER] Ki and G

From: Marek Maly (
Date: Mon Sep 14 2009 - 12:02:36 CDT

Hi Thomas and Bill,

this question is very important also for me and probably
for anybody who do some biological simulations and need
some comparison with experimental data.

Thanks very much to Thomas for his explanation.
I have just one additional question.

Thomas is explicitly speaking about free ENTHALPY of binding, although
Bill is asking about relationship of the total free ENERGY of binding
which has
two components:

dG = dH - TdS

dH: enthalpy part
-Tds: entropy part (complexation "penalty")

Then Thomas used dG, so in my opinion he is speaking also about free
ENERGY of binding
but he made mistake in word descrioption and used ENTHALPY.

Am I right, or the reported formulas really connect just ENTHALPY part of
the binding ENERGY
with binding constant ?

Thanks in advance for explanation.



Dne Mon, 14 Sep 2009 13:59:40 +0200 <> napsal/-a:

> Hi Bill,
> the binding (association) constant Ka of a ligand is connected to its
> free
> enthalpy of binding via
> dG = -RT ln(Ka)
> Most often, its inverse, the dissociation constant Kd is given (just flip
> the sign in the equation above). If the Ki you have is just the binding
> constant of an inhibitor to a receptor:
> E + I <-> EI
> that is all you need. Be aware that in many ligand binding studies,
> competitive inhibition is what's actually measured and the given
> constants
> are IC50 values. In this case, you need to use the Cheng-Prussoff
> equation
> for the conversion:
> IC50 = Ki ( 1 + [L]/kD )
> and the IC50 value depends on the used ligand concentration as well. See
> Cheng et al. Biochem. Pharmacol. 22, 3099-3108 (1973). Also note that
> binding constants are often determined with respect to ph7 and
> physiological ion strength in biochemical systems, which makes a
> difference if the binding involves proton uptake/release.
> So you have to check the experimental data on what they actually measured
> for any comparison.
> Kind Regards,
> Dr. Thomas Steinbrecher
> BioMaps Institute
> Rutgers University
> 610 Taylor Rd.
> Piscataway, NJ 08854
> _______________________________________________
> AMBER mailing list
> __________ Informace od NOD32 4051 (20090504) __________
> Tato zprava byla proverena antivirovym systemem NOD32.

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