Bioinformatics for Vaccinology

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Vaccines: Structural approaches

Ich die Baukunst eine erstarrte Musik nenne.

—Johann Wolfgang von Goethe (1749–1832)

Structure and function

The phrase ‘I call architecture frozen music’, attributed to both Goethe and Frederick Schiller (1759–1805), has been used by Arthur Lesk to highlight both the organizational complexity and aesthetic beauty of protein structures. While many may gainsay the assertion, it is overwhelmingly true that understanding protein function is not possible without understanding protein structure.

Proteins do not evolve as linear sequences, they evolve as objects in three dimensions. That is to say that proteins experience evolutionary pressure as physical objects and not as abstract representations of molecular sequences. We may understand evolution as changes in the lettering of sequences but this is far from how and why it actually occurs. Likewise, we can only conceptualize protein functions at high organizational levels, where they can be interpreted as directly influencing the fecundity of the whole organism. At the molecular level we can only really discuss binding not function. Within the neo-Darwinian paradigm, one may explain biological function in terms of its contribution to an organism's reproductive fitness. However, the idea of fitness reflects the probability of survival in a given environment and can be seen as a basis for selection, although fitness is no more a property of phenotypes than it is of genotypes or the sequences of individual ...