Supporting Information

Horowitz and England 10.1073/pnas.1700617114

This section includes additional analyses of the forcing statis- analysis of Figs. 3 and 4 of the main text for an ensemble of chem-
tics in driven chemical reaction network realizations. In Fig. ical reaction networks in which the driven reaction time con-
S1, the dynamics and forcing statistics are presented for differ- stants are independently sampled. Figs. S2 and S3 demonstrate
ent randomly realized networks that exhibit distinct properties that the effects are robust to additional disorder in the reac-
in their fixed-point ensembles. Figs. S2 and S3 reproduce the tion rates.

Work per Max Current (kT)

40 1.0
2.0 2.6
0.8
Concentration

Frequency
Force (kT)

1.5 30
0.6 2.4
1.0
20 0.4 2.2
0.5
0.2 2.0
10
0.0 0.0
10-3 10-1 10 103 105 107 10-3 10-1 10 103 105 107 10 20 30 40 50 60 10-4 10-2 1 102 104 106
Time (s) Time (s) Force (kT) Time (s)

2.0

Work per Max Current (kT)

65
0.6
12
0.5
Concentration

50 1.5
Frequency
Force (kT)

8 0.4
35
0.3 1.0
4 20 0.2
0.1 0.5
0 5
0.0
-3 -1 3 5 7 -3 -1 3 5 7
10 10 10 10 10 10 10 10 10 10 10 10 20 40 60 80 100 120 140 10-4 10-2 1 102 104 106
Time (s) Time (s) Force (kT) Time (s)

Fig. S1. Comparison of two reaction networks: a network that tends to evolve to a low-force fixed point (Top row) and a network that tends to evolve to
a high-force fixed point (Bottom row). (Left to Right) Representative time evolution of the concentrations of the 25 chemical species: time evolution of the
total thermodynamic force Ftot for 10 different initial conditions, normalized histogram of the total force Ftot from 1,000 uniform samples of configuration
space (orange) compared with the normalized histogram of the total force Ftot attained after 107 s for 500 trajectories with uniform initial conditions
(blue), and work per maximum current η as a function of time for the representative trajectory.

10
Frequency Ratio

2
1
0
0 20 40 60 80 100
Force Percentile Rank
Fig. S2. Characterization of final total forcing Ftot rarity with bare rate constants k and k0 for undriven and driven reactions sampled independently.
Shown is the frequency ratio of the percentile ranks of final total forces Ftot to percentile ranks of uniformly sampled control measured relative to a
uniformly sampled distribution of forces over configuration space. Shading delimits the region where the final total force Ftot occurs less often than the
control. Coloring signifies high-force fixed points (red) and low-force fixed points (blue). Parameters are the same as in Fig. 3 of the main text.

Horowitz and England www.pnas.org/cgi/content/short/1700617114 1 of 2

 103

Driven Force Magnitude

10-1
102

Frequency
-2
10
101
-3
10
1
-4
10
-1.0 -0.5 0.0 0.5 1.0 1 101 102
Pearson Correlation Undriven Force Magnitude
Fig. S3. Characterization of driven and undriven dynamics with bare rate constants k and k0 for undriven and driven reactions sampled independently.
(Left) Normalized histogram of Pearson correlation between driven and undriven force fields, Fdriven and Fundriven , for low-force configurations (orange) and
high-force configurations (blue). (Right) Scatter plot of the magnitude of the undriven force field ||Fundriven || vs. the driven force field ||Fdriven || conditioned
on low-force configurations (orange) and high-force configurations (blue).

Horowitz and England www.pnas.org/cgi/content/short/1700617114 2 of 2