FEATURE ARTICLE
Biomolecules and Nanotechnology
Evolution has forced innovative solutions to biomolecular problems. Some may inform the growing field of nanotechnology
David Goodsell
Biomolecular Self-Assembly
The forces involved in biomolecular structure and interaction are different from those at play in the macroscopic world, and thus our intuition may play us false when attempting to understand protein self-assembly. In our macroscopic world, much of engineering is based on the effect of gravity on solid objects. The strength of concrete and steel and the different frictional properties of Teflon and rubber are familiar quantities.
The molecular world, on the other hand, is dominated by the effect of thermal motion on the atomic interactions within and between molecules. Molecules are endowed with kinetic energy proportional to the temperature, which manifests itself as translational, rotational and vibrational motion. The forces holding molecules together are continually fighting against these motions and are often overcome by them.
The cellular environment is unusual in another respect, as shown in Figure 4. Proteins are synthesized in cells and left to float freely, diffusing to their ultimate site of action amid a crowded collection of competitors. Thus, a typical protein will come into contact with thousands of other types of proteins and must be able to discriminate its unique target from all others. This is quite different from the macroscopic world, where an engineer can selectively fit two parts together. For instance, the concept of a #6 screw would never work inside the cell. When building a chair, we are able to use the same screw to fasten many different pieces together, because we actively choose where each goes. In the cell, however, each molecule must be designed with a unique fastener, ensuring that it binds only to its proper target and no other.
Before atomic structures of proteins were known, physicist H. R. Crane provided two design concepts that are required for biological self-assembly. First, "for a high degree of specificity the contact or combining spots on the two particles must be multiple and weak." An array of many weak interactions, such that all are needed to provide the necessary stability, will form a specific site for interaction. If only a few very strong interactions are used, there is an increased chance that a protein will find a similar interaction with improper proteins.
Second, "one particle must have a geometrical arrangement which is complementary to the arrangement on the other." In other words, the shape of the interacting surfaces must form a good fit, and this fit must be different from that with other proteins. Specificity is provided by the complementary shape of the interacting surfaces, fitting knobs into holes, and by the complementary arrangement of hydrogen-bonding groups and charge-charge pairs. These two principles?that protein-protein interfaces are extended, with many weak interactions, and that protein-protein interfaces are complementary?have been proved in numerous protein structures, such as the one shown in Figure 5.
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