History of Visualization of Biological Macromolecules

On-line Museum

Early Interactive Molecular Graphics at MIT

See animation of "closing" routine

The first system for the interactive display of molecular structures was devised at MIT in the mid-1960s. Taking advantage of Project MAC (Multi-Access Computer), one of the early time-sharing mainframe computers (Fano and Corbato 1966) , Cyrus Levinthal and his colleagues designed a "model-building" program to work with protein structures (Levinthal 1966). This program allowed the study of short-range interaction between atoms and the "online manipulation" of molecular structures. The display terminal (nicknamed Kluge) was a monochrome oscilloscope (figures 1 and 2), showing the structures in wireframe fashion (figures 3 and 4). Three-dimensional effect was achieved by having the structure rotate constantly on the screen. To compensate for any ambiguity as to the actual sense of the rotation, the rate of rotation could be controlled by globe-shaped device on which the user rested his/her hand (an ancestor of today's trackball). Technical details of this system were published in 1968 (Levinthal et al.). What could be the full potential of such a set-up was not completely settled at the time, but there was no doubt that it was paving the way for the future. Thus, this is the conclusion of Cyrus Levinthal's description of the system in Scientific American (p. 52):

It is too early to evaluate the usefulness ofthe man-computer combination in solving real problems of molecular biology. It does seems likely, however, that only with this combination can the investigator use his "chemical insight" in an effective way. We already know that we can use the computer to build and display models of large molecules and that this procedure can be very useful in helping us to understand how such molecules function. But it may still be a few years before we have learned just how useful it is for the investigator to be able to interact with the computer while the molecular model is being constructed.

Shortly before his death in 1990, Cyrus Levinthal penned a short biographical account of his early work in molecular graphics. The text of this account can be found here.

Figure 1. Details of of the CRT screen, with the globe that control the direction and speed of image rotation. Photo courtesy of Martin Zwick. (back)

Figure 2. Overview of the molecular modelling system, with the Kluge in the lower left corner. Notice the space-filling models by the display. Photo courtesy of Martin Zwick. (back)

Figure 3. A display of the structure of the protein lysozyme, showing every fifth amino-acid. Photo courtesy of Martin Zwick.(back)

Figure 4. Details of the structure of myoglobin, showing the heme group with two segments of the polypeptide chain surrounding it. Photo courtesy of Martin Zwick. (back)

See the animation (QT or GIF) of the closing routine applied to a hypothetical peptide chain assumed to consist of several helical sections, where "the individual sections do not bend, but the rotation angles between sections are changed to close the chain into a circle" (Levinthal 1966, p. 50). This animation illustrates the type of routine devised by Levinthal and his collaborators to "model" polypeptide chains. It was created by using a sequence of photographs published in the 1966 Scientific American article. (back)

References

Fano, R. M. and F. J. Corbato(1966). "Time-Sharing on Computers." Scientific American 215(3):128-140.

Levinthal, Cyrus (1966)."Molecular Model-Building by Computer." Scientific American 214(6):42-52.

Levinthal, C., C. D.Barry, et al. (1968). Computer Graphics in Macromolecular Chemistry. Emerging Concepts in Computer Graphics. D. Secrest and J. Nievergelt, Eds. New York,W. A. Benjamin, Inc.: 231-253.