Calibrating and constructing models of protein folding

Abstract

Prediction is more than testing established theory by examining whether the prediction matches the data. To show this, I examine the practices of a community of scientists, known as threaders, who are attempting to predict the final, folded structure of a protein from its primary structure, i.e., its amino acid sequence. These scientists employ a careful and deliberate methodology of prediction. A key feature of the methodology is calibration. They calibrate in order to construct better models. The construction leads to knowledge of how to construct or build an object. Thus, prediction serves a cognitive goal of model construction and not just model or theory testing. The kind of knowledge that results is relevantly different than theoretical knowledge.Keywords Chemistry · Protein folding · Models Although philosophers of science usually list prediction and explanation as important-perhaps even the two most important-epistemic goods provided by science, we pay relatively little attention to prediction. We assume prediction is subservient to explanation, and our account of a worthwhile prediction amounts to not much more than "it matches the data." 1 Yet a normative account of prediction is needed. Many scientists are engaged in predictive modeling, so a philosophical account can provide analyses of the hows and whys of predictive science and thus provide a more complete epistemological analysis of the sciences as a whole. In addition, it is often claimed that predictive models are simply sophisticated "garbage in, garbage out" affairs. Whether this is the exception or the rule must be investigated instead of 1 It is much as if we were to say courage and wisdom are two important character virtues and then proceed to offer an account of wisdom that amounted to only "use your head." Socrates would not be pleased.

Multilevel Research Strategies and Biological Systems

“…Specific research problems-rather than overarching theoriesstructure and make coherent the diversity of approaches employed by researchers, and facilitate systematic evaluations of the resulting contributions (Mitchell 2002;Love 2013Love , 2014Brigandt and Love 2012b). For protein folding, integration among approaches occurs in numerous ways, including organized competitions in which different algorithms for protein structure prediction are tested against structures generated from experimental approaches (Moult et al 1995;Ramsey 2007). Philosophers have to understand how several, multilevel partial representations, which cannot simply be unified, are coordinated and used to inform one another in the context of specific problems rather than for the purpose of constructing or confirming a theory.…”

Calibration: A Conceptual Framework Applied to Scientific Practices Which Investigate Natural Phenomena by Means of Standardized Instruments

“…-which mediate the conversion of raw data issued from the experimental device into claims about natural phenomena. Models, for instance economic models (Boumans 2007), or biochemical models (see Ramsey (2007), who deals with models in protein chemistry).…”

“…Franklin's definition in terms of the use of a surrogate signal works as a reference. It is explicitly mentioned and exploited in many works interested in calibration, including works in which the target of calibration is extended beyond material instrumental devices (see notably Boumans 2004;Harris 2003;Ramsey 2007;Rasmussen 1993;Skipper 2004;Woodward 1989).…”

“…Relying on Franklin's proposal, several other scholars have analyzed calibration in the same perspective. Boumans (2004), Ramsey (2007), Rasmussen (1993), Skipper (2004), Tal (2011), or Woodward (1989) can be seen as examples. These authors have discussed calibration as a potential way to support the reliability of diverse kinds of material or immaterial scientific instruments, in relation to different areas of the natural and the social sciences.…”

Problemas contemporáneos en la filosofía de la bioquímica

“…Por un lado, dentro de las líneas de estudio que podríamos mencionar se encuentran, por ejemplo, la selección causal en el estudio de redes metabólicas (Ross, 2017); las representaciones y explicaciones en la visiones estática y dinámica del alosterismo (Neal, 2021); las clases naturales y el microestructuralismo en el caso de las macromoléculas (e.g. Slater, 2009;Tobin, 2010;Bartol, 2016;Goodwin, 2011;Havstad, 2018;Tahko, 2020); los factores causales que actúan en el plegamiento de las proteínas (Santos et al 2020); el pluralismo y la integración de conocimiento en los modelos sobre proteínas (Mitchell, 2019); el rol de las metáforas en el nacimiento de la enzimología (Mertens, 2019); la estructura de las teorías cinéticas del alosterismo (Alleva et al, 2017); la proposición de una ontología de procesos para entender las macromoléculas (Guttinger, 2018;Alassia, 2022); el problema in-vitro/in-vivo (Strand, 1996(Strand, , 1999Jacob, 2002;Ibarra y Mormann, 2006;García, 2015;Esposito y Vallejos, 2020); y algunos aspectos filosóficos de la predicción de estructura de proteínas (Ramsey, 2007;Mitchell y Gronenborn, 2017).…”