**8-26-24:** Lecture 1 [Course overview]: wiggling and jiggling, the crowded cell, nonequilibrium processes and the origins of life.

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**8-28-24:** Lecture 2: Molecules diffusing in a volume, transition rates for random motion, probabilities, moments, mean squared displacement (MSD).

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**8-30-24:** Lecture 3: Master equation, deriving equations for the moments of the distribution, calculating the MSD.

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**9-4-24:** Lecture 4: Experimentally measuring MSD, diffusion at different biological scales, the implausibility of giraffes, the continuum approximation and the diffusion equation.

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Slides: Shake, rattle, and roll...
Movie: Diffusion experiment
Slides: Diffusion time scales in biology

*Experimental apparatus design:* Bob Sobin, Rick Bihary; thanks to Pete Kernan for the Rokenbok balls

**9-6-24:** Lecture 5: Continuum approximation continued, solving the diffusion and Fokker-Planck equations, the problem of two molecules diffusing to meet in three dimensions.

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**9-9-24:** Lecture 6: Deriving the mean first passage time equation: escape times and probabilties, Frogger, discrete recurrence equation.

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**9-11-24:** Lecture 7: Continuum version of mean first passage time equation, deriving the Smoluchowski rate limit.

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**9-13-24:** Lecture 8: Tradeoff between reaction speeds and cellular crowding.

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Slides: Crowding and the limits of cell size: parasitic bacteria, giant viruses, and seaweed
Movie:

*Random search of a cancer drug for a protein binding site*,

AVI [credits:

Shan *et al.*, J. Am. Chem. Soc. **133**, 9181 (2011)]

**9-16-24:** Lecture 9: Developing a theory of biochemical reaction kinetics, the chemical master equation.

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**9-18-24:** Lecture 10: Chemical master equation in gory detail, approximating chemical dynamics by ignoring fluctuations.

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**9-20-24:** Lecture 11: Connecting transition rates to energy exchange with the environment.

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**9-23-24:** Lecture 12: Probability currents, equilibrium and non-equilibrium stationary states, Boltzmann equilibrium, coupling system transitions to external work.

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**9-25-24:** Lecture 13: Example of coupling to external work source: light-sensitive proteins.

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Slides: Light-sensitive proteins
Movie:

*Photoactive yellow protein in action*,

AVI [credits:

Schotte *et al.*, Proc. Natl. Acad. Sci. **109**, 19256 (2012)]

Movie:

*Optogenetics*,

MP4 [credits:

Nature Methods **8**, 1 (2011)]

**9-27-24:** Lecture 14: Edge and state properties, defining thermodynamic production rates, irreversibility.

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**9-30-24:** Lecture 15: First and second laws of thermodynamics: energy conservation and entropy production; parallels between classical stochastic and quantum systems.

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**10-2-24:** Lecture 16: The "Heisenberg picture" for the classical master equation; proving the existence of a stationary state; the necessity of dissipated power in nonequilibrium stationary states.

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**10-4-24:** Lecture 17: Dissipation in the light-sensitive protein example. Origins of life hypothesis #1: the role of UV photons. Recent advances in prebiotic chemistry.

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Slides: Thermodynamics and the origins of life (part 1).