Interactions:
Obtaining Meaningful
Values with Monte Carlo
Simulations
Simon Chiang
1.0
0.8
0.6
0.4
0.2
0.0 Keq
+
-12 -10 -8
Log [Protein] ΔG = -RT ln Keq
0.8 0.8
0.6 0.6
0.4
0.2 ΔGguess 0.4
0.2 ΔGfit±σGfit
0.0 0.0
Number of Occurences
ΔGfit1
ΔGfit2
ΔGfit3 σ
ΔGfit4
ΔGfit5 Fit ΔG Value
x5000 Single Peak, resolution of a single value
Fit Values over many data sets follow a distribution
with a single peak in probability
Distribution limited near this value (small uncertainty)
Number of Occurences
σσ
Fit Value
Number of Occurences
Fit Program
Fit Value
x5000 No single peak in probability
Number of Occurences
Results of 3 experiments
given by dots
Fit Value
Number of Occurences
Simulated Data Sets
Well-resolved
uncertainties on the data
Number of Occurences
Number of Occurences
vs
σ
Binding Simulator
Program
Binding Curves & Derivatives
• Experiments that monitor
Fractional Saturation
λ repressor dimer
cro gene
(lytic state)
ΔG12 ΔG23
0.8
Site 1
0.6 Site 2
0.4
Site 3
0.2
0.0
number of occurences
number of occurences
-12.8 -12.4 -12.0 -12.0 -11.0 -10.0 -11.0 -10.0 -9.0 -8.0
ΔG1 (σ = 0.1) ΔG2 (‘σ’= 0.5) ΔG3 (‘σ’= 0.5)
number of occurences
number of occurences
<σ> =
kcal/mol
-4.0 -3.0 -2.0 -1.0 -4 -2 0
ΔG12 (‘σ’= 0.5) ΔG23 (‘σ’= 0.5)
• Fit values, uncertainties only meaningful for ΔG1
• ‘standard deviations’ on other parameters are inaccurate
0.8 Site 1
0.6
Site 2
0.4
0.2
Site 3
0.0
-12 -11 -10 -9 -8 -7 -6
Log [ λ repressor dimer]
OR-3 OR-1 -3
number of occurences
number of occurences
number of occurences
-12.8 -12.6 -12.4 -12.2 -10.7 -10.5 -10.3 -9.6 -9.2 -8.8
number of occurences
<σ> =
kcal/mol
-3.2 -3.0 -2.8 -2.6 -3.6 -3.2 -2.8 -2.4
OR-2 OR-1 -3
number of occurences
number of occurences
-12.6 -12.5 -12.4 -10.7 -10.5 -10.3 -9.7 -9.5 -9.3
ΔG1 (σ = 0.05) ΔG2 (σ = 0.06) ΔG3 (σ = 0.06)
number of occurences
number of occurences
<σ> =
kcal/mol
Bain Laboratory
Dr. Aaron Heneghan
Nancy Berton
Michael Miura