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Protein Structure, Dynamics, and Function: A Philosophical Account of Representation and Explanation in Structural Biology

Neal, Jacob P. (2021) Protein Structure, Dynamics, and Function: A Philosophical Account of Representation and Explanation in Structural Biology. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Most philosophical work in molecular biology has historically centered on DNA, genetics, and questions of reduction. My dissertation breaks from this tradition to make proteins the object of philosophical and historical analysis. The recent history of structural biology and protein science offers untapped potential for history and philosophy of science. My ultimate goal for this dissertation therefore is to identify and analyze some of the key historical and philosophical puzzles that arise in these fields. I focus primarily on the shift from the static to the dynamic view of proteins in the late twentieth century. The static view treated proteins as stable, rigid structures, whereas the dynamic view considers proteins to be dynamic molecules in constant motion. In the first half of the dissertation, I develop a historical account of the origins of the static view of proteins. I show how this view led molecular biologists to adopt mechanistic explanation as their preferred strategy for explaining protein function. I then develop an account of the emergence of the dynamic view of proteins, arguing that thermodynamic theory and the theoretical commitments of scientists played an important and often overlooked role in driving this change. In the second half of the dissertation, I analyze the epistemological relationship between the static and dynamic concepts of the protein and argue that conceptual replacement is occurring. I then develop an account of ensemble explanation, a new type of explanation introduced to highlight the role of dynamics in protein function. I show that these explanations fail to fit existing philosophical accounts of explanation, ultimately concluding that my account is required to capture their epistemic structure.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Neal, Jacob P.jpn17@pitt.edujpn17
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee CoChairDietrich, Michaelmdietrich@pitt.edumrd98
Committee CoChairWoodward, Jamesjfw@pitt.edujfw
Committee MemberMitchell, Sandrasmitchel@pitt.edusmitchel
Committee MemberPlutynski,
Date: 8 October 2021
Date Type: Publication
Defense Date: 27 July 2021
Approval Date: 8 October 2021
Submission Date: 6 August 2021
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 243
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > History and Philosophy of Science
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: History of Structural Biology, Protein Dynamics, Structure and Function, Conceptual Change, Theory Change, Ensemble Explanation, Equilibrium Explanation, Mechanistic Explanation, Scientific Representation
Date Deposited: 08 Oct 2021 19:31
Last Modified: 08 Oct 2021 19:31

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