CCL: IC50 deltaG
- From: "elite 158" <elite158(a)gmail.com>
- Subject: CCL: IC50 deltaG
- Date: Mon, 9 Jun 2008 08:47:06 +0530
Thank you very much for updating us on IC50, Ki, DeltaG.
However, I have a very naive question that I couldnt get clarified for so
long. My apologies if the question looks silly.
Scenario: We are working on developing / Identifying new
chemical compounds that can Inhibit a particular enzyme. We however, wanted to
initiate the project by studying already discovered chemical compounds known to
inhibit that enzyme. The next step is to do a computational prediction
based on that information with either QSAR or Pharmacophore or Dcokgins studies.
In various publications we have accessed so far, the biological
activity against the same target enzyme, but of various chemical compounds
is reported as units of IC50, Ki, Ki
app etc.,values. If we need to take
into an account for all the ligands, known to inhibit the target enzyme we are
studying, it makes an absolute requirement that all the activities are reported
as either IC50 or Ki. Upon further research, we came across a KI and IC50
conversion facility through Cheng-Prusoff equation explained clearly in :
However, for the interconvertion, there are no reported radioligand
concentration and kd values that are required by the above mentioned formula.
Question: How do we report the biological activities of
various chemical compounds in various publications as a single consistent
value? i.e., IC50 or Ki. when there is no information available for using the
Any help is highly appreciated..
On Mon, Jun 2, 2008 at 10:35 PM, Michael K. Gilson
Sent to CCL by: "Michael K.
No, you can't assume IC50 is approximately Kd and use DG = RT ln
IC50 is the concentration of inhibitor that leads to half-maximal
inhibition of the targeted enzyme
or receptor. If it is a competitive
inhibitor, then it is competing with substrate (in the case of
an enzyme) or with a labelled ligand (in the case of a receptor). For a given
value of Ki, the value
of IC50 will still vary depending upon how tightly the
substrate or labeled ligand binds the
protein, and also upon its
concentration. The higher the affinity of the substrate or labeled
ligand and the higher its concentration, the more inhibitor will be needed to
have an effect, and
hence the higher IC50 will be -- even though Ki is
The relationship is given by the Cheng-Prusoff equation.
if two inhibitors are assayed for same substrate or labeled ligand and same
thereof, then Delta Delta G = -RT ln r, where r is the ratio of the IC50
(The analysis is different if the inhibitor is not
R D rafi4dd:gmail.com
Sent to CCL by: "R D"
I need a clarification on fundamentals. I want to compare
experimental IC50 values to calculated binding free energy values.
assume IC50 is approx = Kd and use DeltaG = RTlnIC50.
for example if I
want to convert an IC50 value of 1microM it will be equivalent to delta G of
-8.2Kcal/mol. Am I right?
Are we using DeltaG = RTlnIC50 (instead of -RTlnIC50) because we are focused
on dissociation of receptor-ligand complex rather than association of receptor
I apologise if the question is silly, but any reply will be
Michael K. Gilson, M.D., Ph.D.
CARB Fellow and Professor
Advanced Research in Biotechnology
University of Maryland Biotechnology
9600 Gudelsky Drive
Rockville, MD 20850
Lab Page: gilsonlab.umbi.umd.edu