Methods in Molecular Biophysics Structure, Dynamics, Function for Biology and Medicine

HISTORICAL REVIEW

In 1963 Richard Feynman traced to Pythagoras (c.500 BC) the first example, outside geometry, of the discovery of a numerical relationship in Nature. Pythagoras’ discovery, which led to the foundation of a school of thought with mystic beliefs in the power of numbers, was that two strings under the same tension but of different lengths give a pleasant sound when plucked together if the ratio of their lengths is that of two small integers. We now say that a ratio of 1:2 corresponds to an octave, a ratio of 2:3 to a fifth, and so on, which are all harmonic-sounding chords. Feynman analyzed this discovery in terms of three characteristics: its basis in experimental observation; the use of mathematics as a tool for understanding Nature; and its concern with aesthetics (the “pleasant” quality of the sound). With easy hindsight (as he readily admits!) Feynman wrote that if Pythagoras had been more impressed by the first point on the importance of experimental observation the science of physics might have had an earlier start.

We discovered the existence and seek our biophysical understanding of macromolecules through experimentation, and we use mathematical tools not only to set up experiments and analyze the results, but also for the description of the studied “objects” themselves. The basis of aesthetics may still remain as mysterious as in Pythagoras’ time, but there is no doubt that the “beauty” of the DNA double helix and the satisfyingly elegant way in which it provided an explanation for how genetic information is stored and transmitted was an essential inspiration in the development of modern molecular biology. Similarly, the usual, colorful illustrations of protein structural models are undoubtedly aesthetic and certainly play a role in the acceptance and understanding of these models by biologists, who might have been put off by a purely mathematical interpretation of the data, even if it were more accurate.

Experiments on biological macromolecules are difficult to perform and interpret. Sample material is fragile and a good biophysical experiment must rest on a firm biochemical foundation. Biological macromolecules are much smaller than the wavelength of light and cannot be “seen.”