The fifth meeting of BIG saw the presentation of a draft-paper by Stephan Guttinger. His paper, entitled ‘From Practice to Process’, examines how several practices in molecular protein biology have encouraged a view of the nature of proteins that misleadingly reconceives them, changing them from the process-like entities that are encountered in practice and experiment, into thing-like entities when posited in theoretical models. For instance, the author observes that to consider protein microstructure as thing-like is at a discord with the experimental practices from which such assertions are derived, e.g. maintaining protein microstructure is technically difficult, since it is highly dynamic and fragile to sustain in vivo (cf. ‘protonation states’).
The molecular level of biology is often seen as a significant challenge for process ontologists. More specifically, the sequence-structure-function paradigm (SFF) of protein nature and behaviour could be seen supporting the idea that proteins exist substantially as things (and not processually). As the author explains, the SFF paradigm consists of two key claims: (1) the protein exists as its three dimensional structure (or “fold”) and this fold causes the protein’s function; (2) the fold exists as the amino acid sequence and this sequence, often called the ‘primary structure’ or ‘microstructure’, causes the structure of the fold to form (for a review, see Keskin et al., 2008). For example, for a protein to interact with another protein, such an action depends on the presence of corresponding acidic or hydrophobic patches on the surface of the corresponding protein – this is often referred to as “the hand-and-glove model” (Koshland, 1958), which is itself a play on Fischer’s famous lock-and-key analogy (1894). In a similar way, enzymes are acknowledged as displaying a structure, within a region designated as the “active site”, which corresponds with the structure of their substrate.
However, as the author indicated, an understanding of proteins based on the SFF paradigm has been threatened by cases of Intrinsically disordered proteins (Dunker et al., 2001; Dyson & Wright, 2005; Uversky & Dunker, 2010). The author asks whether this change in understanding necessitates a transformation in the underlying ontological assumptions also, and thereby undermining one of the last bastions of a substance ontology in biology. IDPs are explicated as having no fixed three-dimensional structure in their native state, and that this can be true of a part of a polypeptide chain or it can be true of its whole length. The author characterised the disorder of IDPs along three dimensions: (1) the intensity of the disorder (i.e. at one end of the scale the IDP exhibits complete disorder, allowing its amino acids the maximum freedom of movement that its covalent bonds allow for, but at the other end the IDP exhibits ‘molten-globule-like’ disorder, which represents a hybrid state between a fully ordered state and a random-coil); (2) the extent of the disorder (i.e. whether it is localised to a short stretch, a single domain, or the whole length of a protein); and (3) the relation between the disordered state and the functional state of the protein.
The group discussed the giddiness of extrinsic and intrinsic relations in the context of grounding the two ontologies, and we attempted to provide some analytical distinctions of the important concepts in play. It would seem typical to a substance ontology that an existing substance is grounded in its essential characteristics. In some sense it might be said that the essence is intrinsic to its substance. It might then seem to follow from this that the relations between substances are accidental upon that which determines a substances existence; in other words, the existence of a substance is somewhat independent of its extrinsic relations. Contrarily, if a process (and not a substantial entity) is all that can be said to exist, what was once ascribed as its essences becomes an effluence, undergoing indefinite changes. For a process ontology then, relations are constitutive of their existence; a process’ relations are essential to its existence.
The author situates his discussion within two philosophical projects, whose concerns converge in the case he examines. With regards to the first project, proponents wish to provide the intellectual resources that brings our thinking towards a naturalistic metaphysics, specifically the author examines the dispute between a substance ontology and a process ontology; in the second project, proponents bring renewed attention towards scientific practices as something which is as important for scientific understanding as theory building. Specifically the author examines how the practices of some cases of protein science inform discussions concerning metaphysical assumptions. In effect, the author argues, what some scientists model as the (theoretical) nature of proteins is antagonistically opposed to how they are treated practically and experimentally. Moreover, the author argues that it is because the substance ontology is deeply embedded in the received thinking of the sciences that this juxtaposition and contradiction between the theory and practice of protein science has endured; but, as the author believes, this problem is overcome when the practices of these scientists are sufficiently exposed.
Dunker, A.K., J.D Lawson, C.J. Brown, R.M. Williams, P. Romero, J.S. Oh, C.J. Oldfield, A.M. Campen, C.M. Ratliff, K.W. Hipps, & J. Ausio, ‘Intrinsically disordered protein’, Journal of Molecular Graphics and Modelling, 19:1 (2001) 26-59
Dyson, H.J., & P.E. Wright, ‘Intrinsically unstructured proteins and their functions’, Nature Reviews Molecular Cell Biology, 6:3 (2005) 197-208
Fischer, E., ‘Einfluss der Configuration auf die Wirkung der Enzyme’, Berichte der deutschen chemischen Gesellschaft, 27:3 (1894) 2985-2993
Keskin, O., A. Gursoy, B. Ma, & R. Nussinov, ‘Principles of protein-protein interactions: what are the preferred ways for proteins to interact?’, Chemical reviews, 108:4 (2008) 1225-1244
Koshland, D.E., ‘Application of a theory of enzyme specificity to protein synthesis’, Proceedings of the National Academy of Sciences, 44:2 (1958) 98-104
Uversky, V.N. & A.K. Dunker, ‘Understanding protein non-folding’, Biochimica et Biophysica Acta (BBA) – Proteins and Proteomics, 1804:6 (2010) 1231-1264