The 50th anniversary of the classic Monod–Wyman–Changeux (MWC) model provides an opportunity to survey the broader conceptual and quantitative implications of this quintessential biophysical model. With the use of statistical mechanics, the mathematical implementation of the MWC concept links problems that seem otherwise to have no ostensible biological connection including ligand–receptor binding, ligand-gated ion channels, chemotaxis, chromatin structure and gene regulation. Hence, a thorough mathematical analysis of the MWC model can illuminate the performance limits of a number of unrelated biological systems in one stroke. The goal of our review is twofold. First, we describe in detail the general physical principles that are used to derive the activity of MWC molecules as a function of their regulatory ligands. Second, we illustrate the power of ideas from information theory and dynamical systems for quantifying how well the output of MWC molecules tracks their sensory input, giving a sense of the “design” constraints faced by these receptors.

Renewal processes are broadly used to model stochastic behavior consisting of isolated events separated by periods of quiescence, whose durations are specified by a given probability law. Here, we identify the minimal sufficient statistic for their prediction (the set of causal states), calculate the historical memory capacity required to store those states (statistical complexity), delineate what information is predictable (excess entropy), and decompose the entropy of a single measurement into that shared with the past, future, or both. The causal state equivalence relation defines a new subclass of renewal processes with a finite number of causal states despite having an unbounded interevent count distribution. We use the resulting formulae to analyze the output of the parametrized Simple Nonunifilar Source, generated by a simple two-state hidden Markov model, but with an infinite-state -machine presentation. All in all, the results lay the groundwork for analyzing more complex processes with infinite statistical complexity and infinite excess entropy.

Loosely speaking, the Shannon entropy rate is used to gauge a stochastic process' intrinsic randomness; the statistical complexity gives the cost of predicting the process. We calculate, for the first time, the entropy rate and statistical complexity of stochastic processes generated by finite unifilar hidden semi-Markov models-memoryful, state-dependent versions of renewal processes. Calculating these quantities requires introducing novel mathematical objects ( -machines of hidden semi-Markov processes) and new information-theoretic methods to stochastic processes.