Abstract. Different chemical species are often cited as paradigm examples of structurally delimited natural kinds. While classificatory monism may thus seem plausible for simple molecules, it looks less attractive for complex biological macromolecules. I focus on the case of proteins that are most plausibly individuated by their functions. Is there a single, objective count of proteins? I argue that the vagaries of function individuation infect protein classification. We should be pluralists about macromolecular classification. (..) Counting proteins by structures or by functions? (..) structure: primary (amino acid sequence), secondary (e.g., a-helices and b-pleated sheets), tertiary (three-dimensional folding), quaternary (multiple folded subuntis complexed together). (..) The same amino acid sequence can be folded into a variety of different tertiary structures with different biochemical dispositions and functions (..) due to different contexts and different interactions. (..) X-ray crystallographic "snapshots" no more capture the essence of a protein than a single satellite photo does of a hurricane. (..) Proteins are structures in motion. (..) Emil Fischer’s long-standing static "lock-and-key" model of enzyme-substrate interaction has been replaced by Koshland’s (1958) "induced-fit" model. For Fischer’s model makes sense of the target specificity of proteins but not their enzymatic activity. As Matthews and van Holde put it, "a lock does nothing to its key" (1996, 368). (..) whereas we thought there were around 100,000 proteins in the human body, there may in fact be continuum-many. (..) stance "dappled structuralism" we might call it "picking out primary sequences in some cases and (somehow) tertiary structures in others" (..) coheres less well with scientific practice (..) e.g. ADH comes in many "alleloforms" - very slightly different polypeptide sequences whose differences happen to be inconsequential to the protein’s tertiary structure and biochemical function. (..) The very same polypeptide sequence might get differently folded within a cell membrane to function in signal transduction or as a transcription regulator within different cells. How many kinds of proteins have we here? (..) However we understand biological function, ascription of function will likely be a holistic enterprise. This gives rise to a deep and theory-neutral pluralism. (..) Broadly speaking, two approaches to function have dominated the literature: the etiological or selected-effects approach (championed byWright [1973], Millikan [1984, 1989], and Neander [1991]) and the causal role or systemic-capacity functions (developed by Cummins [1975], Amundson and Lauder [1994], and Davies [2001]). (..) According to the selected-effects approach, the function of a trait depends on whether performance of that function has figured in the selective history of that trait. (..) the more liberal systemic-capacity approach attempts to understand the function of a component in terms of its contribution to the capacities of the larger system. (..) How many kinds of proteins are in the typical human body? Perhaps there is an answer in that it has many answers. Is there then any point to calling any of these answers correct? (..) As yet, I think we have only the slimmest grasp on how to unite pluralism with some sense of realism. (..) Pluralism makes good sense of the actual classificatory activities of biochemists. Our classification schemes typically reflect our best inductive and explanatory strategies - and these are rarely neat and tidy. (..) Biochemists can avail themselves of a plurality of legitimate classificatory systems simultaneously by invoking what I’d like to call different "modes" of classification. e.g. ADH: the same kind of enzyme is actually a class of two kinds of polypeptides. (..) Polypeptides are individuated by their sequence (..) enzymes (and proteins more generally) are individuated, at least in large measure, by their function. (..) While these different modes may cross-classify reality (or merely reveal different "layers" of structure), they need not be regarded as forcing hard choices. (..) Our rich system of different interleaved levels of functional and structural classification, I think, is best understood as the result of coming to terms with the genuine plurality of systems of functional and structural kinds. I suggest that we look to the role of organizing terms in our conceptualization of the world. There is no dividing the world into the natural kinds, perhaps - but that doesn’t mean that there aren’t natural kinds. There are natural kinds of enzymes, natural kinds of polypeptides, natural kinds of organisms, natural kinds of celestial objects, and so on - each dependent on norms of classification devolving from our best inductive and explanatory practices. |