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I have a problem with two (or more) proteins binding to a receptor. The only measurement I have
is total unbound protein after addition of the a known amount of binding compound, I don't know the
ratio of the proteins either before or after the addition of the binding compound. If this were one
protein, it would follow the usual dissociation relationship:
relationship. From this I can calculate everything (AB is related to the change in total protein
before and after, and A+AB (molar) = the total protein before, B+AB (molar) = total binding compound
before, and I can calculate everything and estimate Kd
Any suggestions on how to do this with two proteins? The plot of total binds vs remaining total
protein drops more quickly as dose increases from low doses (i.e., underpredicts the low doses,
higher remaining protein), but then over predicts the high doses (lower remaining total protein).
So, I'm suspecting two proteins with different Kds.
Any suggestions would be helpful
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From your description it is not clear whether this is in-vitro system
(where all is defined by the binding) or in-vivo (where elimination
plays role). Also, notations are not clear: seems like you use "protein"
for both receptor and the ligand.
Assuming that you have in vitro system with two drugs A and B that can
bind the same target C, you can write (at equilibrium)
Then the total target (is this what you call total binds?) is C + AC +
BC while total drugs (total proteins?) is A+B+AC+BC
For the in vitro system you should know all amounts, so
A + AC = Atot (3)
B + BC = Btot (4)
C + AC + BC = Ctot (5)
So you have 5 equations for 5 quantities (A, B, C, AB, AC). If you know
KD1, KD2, Atot, Btot, Ctot, you can compute everything. If you do not
know KD1 and KD2 but can measure some combinations (other than Atot,
Btot, and Ctot), you can derive KD1 and KD2.
Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
e-mail: LGibiansky at quantpharm.com
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