The Physics of Proteins: An Introduction to Biological Physics and Molecular Biophysics; Theoretical Molecular Biophysics

The Physics of Proteins: An Introduction to Biological Physics and Molecular Biophysics, Hans Frauenfelder (edited by Shirley S. Chan and Winnie S. Chan) Springer, New York, 2010. $159.00 (448 pp.). ISBN 978-1-4419-1043-1

Theoretical Molecular Biophysics Philipp O. J. Scherer and Sighart F. Fischer Springer, New York, 2010. $99.00 (371 pp.). ISBN 978-3-540-85609-2

Since biophysics is a young science, its major emphasis has been on experiment rather than theory. However, theory is necessary to provide the broad outlook that welds experimental results into a cohesive picture; it may also suggest new experiments. Two new books should help reduce the theory deficit.

The Physics of Proteins: An Introduction to Biological Physics and Molecular Biophysics contains lecture notes by biophysicist Hans Frauenfelder; it is edited by Shirley Chan and Winnie Chan and has contributions from four physicists in the field: Robert Austin, Charles Schulz, Ulrich Nienhaus, and Robert Young. It appears to be written for advanced undergraduates and graduates in physics who are newcomers to biophysics and biochemistry. Frauenfelder completed his doctoral degree in 1950 at ETH Zürich, where he studied under Paul Scherrer, Wolfgang Pauli, and Gregor Wentzel. He then moved to the University of Illinois at Urbana-Champaign where for the next four decades he conducted research on the dynamics of proteins, measuring their response to a pulse of synchrotron radiation over broad ranges of temperature and time. Those experiments revealed the multiple, nonrigid configurations inherent in proteins and led him to appreciate their complexity. Since 1990 he has continued his research at Los Alamos National Laboratory.

Following the introductory chapters, the book discusses the three-dimensional structure and dynamics of proteins, particularly myoglobin and hemoglobin. The book builds from Frauenfelder’s sketches and hand-drawn diagrams, which impart to the volume a personal touch, to its major theme: Frauenfelder’s insight that protein structures undergo conformational transitions—proteinquakes—through substates of approximately equal energy in a rugged, multidimensional, conformational-energy landscape.

In a beautiful example of the interplay of theory and experiment, the discussion of electronically controlled reactions in the chapter on reaction theory gives an atom-by-atom account of the concerted motion of nuclei and electrons that occurs when carbon monoxide binds to the iron atom at the center of a hemoglobin molecule’s heme group. Informative appendices cover thermodynamics, quantum chemistry, Mössbauer spectroscopy, nuclear magnetic resonance, and x-ray and neutron diffraction. The other contributors highlight some of the challenges in the field: “We have a long way to go” in deciphering the structural dynamics of the T4 lysozyme, Austin cautions on page 433. Readers are also encouraged in chapter 17, “Creative Homework: Dynamics and Function,” to dig into the dynamics, processes, and functions of neuroglobin (Nienhaus) and of the folding of a polypeptide chain into a functional protein (Young). Each chapter closes with a list of references.

Some aspects of The Physics of Proteins left me puzzled. Although claiming interest in “a fundamental understanding of . . . essentially all proteins” (page 209), the book omits an important class of them—membrane proteins. In chapter 14, “Supercooled Liquids and Glasses,” Frauenfelder asserts that “many properties of glasses and proteins are similar.” But are there glassy proteins at physiological temperatures? Particularly perplexing were Austin’s discussions of Davydov solitons in chapter 16, “Protein Quantum Dynamics?” In the theory part, Austin dismisses that model, asserting that “most biological polymers are insulators.” However, that is true only for electronic conduction, not ionic conduction, an important mechanism in cellular respiration, information processing, and force generation. Also, in a chapter on water, Austin proves the nonexistence of ferroelectricity in ice but ignores ferroelectricity in liquid crystals and proteins.

Intended for graduate students, Theoretical Molecular Biophysics by Philipp Scherer and Sighart Fischer grew out of a biophysics course taught by the authors in the physics department of the Technical University of Munich. This well-organized book assumes familiarity with such mathematical objects as symmetry groups, the delta function, and raising and lowering operators. In the preface, Scherer and Fischer point out that “while the biologist uses mostly a phenomenological description, the physicist tries to find the general concepts to classify the materials and dynamics which underly [sic] specific processes.” They also note that although biological systems exhibit “a certain amount of disorder,” their functions, paradoxically, “are highly reproducible.” The challenge of the book, which lists 132 references, is to “try to provide basic concepts, applicable to biological systems or soft matter in general.”

A striking feature of Theoretical Molecular Biophysics is the large number of equations relative to text, with a sampled average of 7.3 lines of equations per page, far more than the 1.6 in Frauenfelder’s book. That wealth of equations comes at the expense of text. The few terse sentences that constitute the leading paragraphs of chapters deliver little biological perspective or historical background. Nevertheless, links provide thematic continuity across chapters in the sections on statistical mechanics of biopolymers, protein electrostatics and solvation, reaction kinetics, transport processes, and reaction rate theory. Most chapters close with challenging problems whose solutions are provided at the end of the book.

The book’s flagship chapters address coherent excitations in photosynthetic systems, ultrafast electron transfer processes in the photosynthetic reaction center, and proton transfer in biomolecules such as bacteriorhodopsin. Those chapters contain derivations, calculations, structure diagrams, and comparisons of predictions with experimental results. In spite of its importance in the text, the word “photosynthesis” does not appear in the index. The book closes with an interesting review of molecular-motor models.

When Scherer and Fischer assert on page 195 that “translational . . . motion . . . is essentially hindered for Biomolecules in the condensed phase,” they appear to ignore the sliding motion of actin and myosin in muscle contraction. Also, in chapter 12, “Ion Transport Through a Membrane,” the authors recall an analogy between “diffusion and reaction” and electronic circuit theory, based on the brilliant 1952 model by Alan Hodgkin and Andrew Huxley. However, as I discuss in my book, Voltage-Sensitive Ion Channels: Biophysics of Molecular Excitability (Springer, 2008), contemporary models are based on a more complete knowledge of the excitable membrane and the protein molecules embedded in its lipid bilayer that selectively carry ions through the membrane under voltage control. Without a mention of those macromolecules, which have been isolated, cloned, and characterized through genetic engineering, the discussion of ion transport is out of date.

Chirality is not discussed in either Theoretical Molecular Biophysics or The Physics of Proteins; phase transitions are mentioned only in Scherer and Fischer’s chapter on solutions. Thus the books fail to consider such concepts as the order parameter, soft modes, and domain formation; a good supplement to either would be Minoru Fujimoto’s The Physics of Structural Phase Transitions (2nd edition, Springer, 2005). However, the two works do provide an abundance of physics-based insight into the structures, transitions, and functions of the molecules of life. If, as Austin predicts, “We can expect exciting progress [in the physics of biomolecules] in the next few decades,” the books should play important pedagogical roles. Nevertheless, even though the two books are dedicated to similar goals, the disparity in their topics and approach suggests that the budding romance between theoretical physics and protein science has many difficulties to overcome before it can flower.