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Ligand-receptor binding as a chemical reaction

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Presentation on theme: "Ligand-receptor binding as a chemical reaction"— Presentation transcript:

1 Physics 414: Introduction to Biophysics Professor Henry Greenside September 19, 2017

2 Ligand-receptor binding as a chemical reaction

3 How to measure binding energies experimentally

4 Ligand-receptor binding data (Fig 6.28, p. 273)
Oxygen binding to myoglobin Repeat finding minimum Kd for different temperatures and then use relation: HIV protein binding to cell receptor CD4

5 Raw data from journal article “Studies on the O2 and CO Equilibria of Human Myoglobin”, A. Rossi-Fanelli and E. Antonini, Arch Biochem and Biophy 77:478 (1958) Used to generate Fig 6.28(A) of PBOC2

6 Raw data from journal article “Studies on the O2 and CO Equilibria of Human Myoglobin”, A. Rossi-Fanelli and E. Antonini, Arch Biochem and Biophy 77:478 (1958)

7 Mathematica notebook for obtaining and fitting data from a journal figure
Use screenshot to grab figure as PNG Import or paste PNG into Mathematica Use Coordinates Tool to grab data points from figure in pixel coordinates. Use Coordinates Tool to grab points corresponding to tickmarks on x axis, and separately for tickmarks on y axis Use Mma Fit to fit lines that convert pixel coordinates to scientific coordinates, one for x, one separately for y Use these functions to convert data pixel coordinates to scientific coordinates. Finally use Mma NMinimize to fit function of desired type (such as Langmuir isotherm) to scientific data by minimizing a least-squares function.

8 Can get cooperative switching-like behavior by binding multiple ligands
Note assumption that we can ignore intermediate binding of one ligand to R so [LR] doesn’t appear. You justify this in homework problem, that intermediate states are rare compared to final state.

9 Hill function for different Hill coefficients n
Now have two parameters to fit to data, Kd and n, can use Mathematica function NMinimize to get approximate local minimum

10 One-minute End-of-class Question


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