Gabriel Vallejos Baccelliere

The protein folding problem is one of the foundational problems of biochemistry and it is still considered unsolved. It basically consists of two main questions: what are the factors determining the stability of the protein’s native structure and how does the protein acquire it starting from an unfolded state. Since its first formulation, two main explanatory approaches have dominated the field of protein folding research: a thermodynamic approach focused on energetic features and a kinetic approach focused on the temporal development of protein chains and structural considerations. Although these two approaches are tightly intertwined in biochemical practice and largely agree on which are the parts and activities in which the phenomenon under study should be decomposed to, there nevertheless exist important contrasts that have had repercussions on the development of the field and still engender vigorous debate. We shall analyse the historical development of the field and crucial aspects of current scientific debates. On this basis, we argue that the main sources of disagreement centre on the causal interpretation of thermodynamic and kinetic explanations, on the explanatory relevance assigned to different features of the phenomena under study and on the status of the ontological assumptions concerning the entities under study.

Si bien en la filosofía de las ciencias ya se han explorado algunos ejemplos provenientes de la bioquímica como casos de estudio, la filosofía de la bioquímica es una subdisciplina naciente. En este artículo estudiaremos dos problemas filosóficos de relevancia contemporánea en esta ciencia. Por un lado, examinaremos las bases epistemológicas del problema del plegamiento de proteínas. En particular lo relacionado con la predicción de la estructura tridimensional de las proteínas a partir de su secuencia, asunto que ha dado mucho que hablar debido a los nuevos avances utilizando deep learning. Por otro lado, exploraremos el problema in-vitro/in-vivo y, más generalmente, el problema de la extrapolación en las ciencias biológicas. Finalmente, a partir de las consecuencias de ambos temas consideraremos algunas reflexiones filosóficas generales acerca del reduccionismo, el pluralismo y el lugar de la bioquímica en las ciencias biológicas. Palabras clave: Bioquímica, Plegamiento de proteínas, In-vitro/in-vivo, Pluralismo, Reduccionismo.

One of the foundational problems of biochemistry concerns the conceptualisation of the relationship between the composition, structure and function of macromolecules like proteins. Part of the recent philosophical literature displays a reductionist bias, that is, the endorsement of a form of microstructuralism mirroring an out-dated biochemical conceptualisation. We shall argue that such microstructuralist approaches are ultimately committed to a potentialist form of micro-predeterminism whereby the macrostructure and function of proteins is accounted for solely in terms of the intrinsic properties and potentialities of the components of the primary structure as if they were self-contained or essentially immutable entities. We shall instead suggest that a conceptualisation of the relationship between proteins’ composition, structure and function consistent with contemporary biochemical practice should account also for the causal role of the cellular, organismal and environmental relations in protein development. The analysis of the folding process we propose suggests that microstructure-laden reductionist approaches are ontologically indefensible. Rather than a potentialist form of micro-predeterminism, our analysis ultimately supports a relational-construction-based view of protein development and potentialities formation, which requires an indispensable analysis of the dynamical interplay between the micro-level of the parts and the macro-level of the relational structures of their systems.