Biology is often taught with diagrams. But you can also teach it with equations, the language of physics. In his new book, The Molecular Switch: Signaling and Allostery, biophysicist Rob Phillips does just that, explaining allostery—a biological enigma—using the formalism of statistical physics.

Many proteins can be analogized to simple switches with on and off states, like the ones present on the US Capitol’s switchboard, pictured here in 1959.

Many proteins can be analogized to simple switches with on and off states, like the ones present on the US Capitol’s switchboard, pictured here in 1959.

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Phillips is a professor of biophysics, biology, and physics at Caltech. He has authored or coauthored several books that creatively combine concepts from biology, physics, and materials science, including Crystals, Defects and Microstructures: Modeling Across Scales (2001); Physical Biology of the Cell (2nd edition, 2012); and Cell Biology by the Numbers (2016). The Molecular Switch is another fantastic book in that vein. It is an elegant demonstration of how physics can be used to explain a biological concept and unify a wide range of biological phenomena. The book is a great introduction to biophysics for both physicists and biologists and a versatile reference for advanced undergraduate and graduate biophysics courses.

Proteins are the building blocks and functional molecular units of living cells. For cells to operate properly, proteins must function in a controlled manner. But how do they do that? Richard Feynman acknowledged in his 1963 lectures on physics that “everything that living things do can be understood in terms of the jigglings and wigglings of atoms.” His maxim also holds true for proteins. They fold into elaborate three-dimensional structures and can interact with other molecules. Those intra- and intermolecular changes are dynamic and affect a protein’s function over time.

If its activity changes on the binding of a small molecule, a protein is said to be allosteric, a term originally coined by Jacques Monod and François Jacob in 1961. Many, if not all, proteins are expected to be allosteric. Because its consequences are so profound, allostery has been called the second secret of life after the genetic code.

Despite its broad impact in the field, allostery is explained rather briefly in most biology textbooks, with just one example—namely, the cooperative binding of oxygen in hemoglobin, the protein that carries the molecule in our blood. The primary achievement of Phillips’s new book is twofold: It expands the discussion of allostery to almost everything in nature and suggests a new paradigm for studying it.

As illustrated on the book’s cover, that new paradigm is based on switches. Because many proteins can be likened to switches with on and off or active and inactive states, cellular functions can be viewed as input–output responses of those molecular switches. The switch analogy allows biophysicists to ignore the microscopic details of different allosteric molecules and analyze protein functions in terms of discrete states through the formalisms of equilibrium statistical physics.

Using that paradigm, Phillips aims to communicate with audiences from both biology and physics. He tactfully achieves that goal through his straightforward and logical organization. In chapters 1 and 2, Phillips explains allostery from the perspectives of biology and physics so that all readers are on the same page. He lays out basic statistical-physics concepts so that his model can be easily derived. In chapter 3, he uses the simple example of ion channels to demonstrate how statistical physics can be used to describe a molecular switch and experimentally measurable behaviors such as leakiness and dynamic range.

Phillips then applies that formalism with depth, breadth, and clarity to various biological topics, including the swimming of bacteria in response to a chemoattractant, cell signaling in such processes as photon detection in the eye, and gene regulation by transcription factors or nucleosomes. Those examples are presented not as information to be memorized but as a series of applications of the mathematical framework presented in the earlier chapters. Phillips also takes readers over multiple scales of biology, from animals to cells and molecules, and thus highlights the significance and universality of allostery in nature.

Teaching a biophysics course can be challenging because students have mixed backgrounds and expectations. Students from physics may be overwhelmed by biological details, which can prevent them from seeing biophysics’ bigger picture. On the other hand, students from biology might feel frustrated by physics equations. The Molecular Switch serves students from both fields, who will be happy to see that a simple physical model can explain so many different and seemingly disparate phenomena. Another educational benefit of the book is that it teaches students how to develop effective theories to describe biological phenomena, which will be crucial for future collaborations between physicists and biologists.

The concept of allostery has been around for several decades. But who would have thought it could be used to create a physical law that unifies biology? Phillips does just that in The Molecular Switch. Anyone who likes the beauty of unification will appreciate his ingenious approach.

Sangjin Kim is an assistant professor in the department of physics at the University of Illinois at Urbana-Champaign. She uses biophysical approaches to study the mechanism of DNA allostery and its implications on gene expression.