After Fifty Years, Why Are Protein X-ray Crystallographers Still in Business?

It has long been held that the structure of a protein is determined solely by the interactions of the atoms in the sequence of amino acids of which it is composed, and thus the stable, biologically functional conformation should be predictable by ab initio or de novo methods. However, except for small proteins, ab initio predictions have not been successful. We explain why this is the case and argue that the relationship among the different methods, models, and representations of protein structure is one of integrative pluralism. Our defence appeals to specific features of the complexity of the functional protein structure and to the partial character of representation in general. We present examples of integrative strategies in protein science.