Book Review: Proteins: A Theoretical Perspective of Dynamics, Structure, and Thermodynamics

This treatise, published as Vol. LXXI of the Advances in Chemical Physics series, is an enlightening introduction to the new and rapidly developing field of molecular dynamics of proteins. Written in clear language, with relatively few equations and a comprehensive reference list, it discusses methodology and numerical procedures applied, elaborates on the major results obtained to date, and concludes with a comparison between molecular dynamics calculations and experiment. In the methodology section, the authors cover the semiempirical potential energy functions and the variety of dynamical simulation techniques (classical and stochastic trajectories, normal mode analysis, and Monte Carlo energy minimization) as they apply to proteins. The authors are careful to point out both merits and possible pitfalls in the various methods. Results obtained in several groups are logically organized in a hierarchial fashion: From small motions of side chains, through larger backbone motions, to large motions of rigid structures, e.g., double helices and domains. Hence the incredibly complex motions in proteins unfold for longer and longer time scales. The influence of additional solvent molecules on the vacuum simulations is discussed. The qualitative agreement with experiment of such detailed calculations is remarkable. It is noted that the theoretical results actually contain much more information than can conceivably be generated by experiment. Although barely older than one decade, the field of protein dynamics has already changed our concept of proteins dramatically. While the impression given by classical X-ray studies is of rigid, well-defined protein structures which are all-important to their function (i.e., the lock-and-key picture for enzyme-substrate activity), it is becoming increasingly clear from molecular dynamics simulations that protein fluctuations can have relatively large magnitudes and that these play a crucial role in protein activity. This is observed for all length and time scales: The rotation of a