Protein folding as a configurational reconstruction: Bio-epistemic application of the General Epistemic Dispersion Theory to adult human hemoglobin

This repository includes a theoretical extension of the General Epistemic Dispersion Theory (GEDT) formalism to the domain of molecular biology, using adult human hemoglobin (HbA) as a case study. The manuscript proposes a bio-epistemic mapping in which the acquisition of the three-dimensional configuration is analyzed through the conditional decomposition of configurational uncertainty.Within this model, the primary sequence acts as a reusable structural core (S), while specific dynamic interventions, such as chaperone assistance (e.g., AHSP for a-globin), can be formalized as additional information required to resolve residual uncertainty. Main additions in this release: Evolutionary interpretation of structural constraint (Section 12): We introduced an analysis that frames evolutionary selection as a process that progressively shapes primary sequences and recurrent structural constraints. The framework suggests that evolutionary history may reallocate part of the configurational burden from execution-specific dynamics to reusable structural information encoded in S, thereby restricting the feasible configuration space. It is formally clarified that this perspective implies neither teleological optimization nor the explicit minimization of a GEDT-defined cost function. Application Limitations and Methodological Cautions: The present work is definitional in purpose and not substitutive. As explicitly stated in the text: The manuscript introduces no new biochemical mechanisms and presents no new experimental biological data. The framework does not propose an alternative to thermodynamics, kinetics, or structural biology; rather, it operates at a different descriptive level, focusing on the allocation of the informational burden required to determine a global configuration. The quantification of the biological residue and additional information strictly depends on the adopted model boundaries. The objective is to provide a falsifiable informational language to outline a program for future quantitative verification

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Publication Details

Journal
Zenodo (CERN European Organization for Nuclear Research)
Published
2026-09-29
DOI
https://doi.org/10.5281/zenodo.23036027
Primary Topic
Hemoglobin structure and function
Type
preprint
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preprint

Protein folding as a configurational reconstruction: Bio-epistemic application of the General Epistemic Dispersion Theory to adult human hemoglobin

Massimo Comitato
Zenodo (CERN European Organization for Nuclear Research)
Hemoglobin structure and function
preprint

Protein folding as a configurational reconstruction: Bio-epistemic application of the General Epistemic Dispersion Theory to adult human hemoglobin

Massimo Comitato
preprint en

Abstract

This repository includes a theoretical extension of the General Epistemic Dispersion Theory (GEDT) formalism to the domain of molecular biology, using adult human hemoglobin (HbA) as a case study. The manuscript proposes a bio-epistemic mapping in which the acquisition of the three-dimensional configuration is analyzed through the conditional decomposition of configurational uncertainty.Within this model, the primary sequence acts as a reusable structural core (S), while specific dynamic interventions, such as chaperone assistance (e.g., AHSP for a-globin), can be formalized as additional information required to resolve residual uncertainty. Main additions in this release: Evolutionary interpretation of structural constraint (Section 12): We introduced an analysis that frames evolutionary selection as a process that progressively shapes primary sequences and recurrent structural constraints. The framework suggests that evolutionary history may reallocate part of the configurational burden from execution-specific dynamics to reusable structural information encoded in S, thereby restricting the feasible configuration space. It is formally clarified that this perspective implies neither teleological optimization nor the explicit minimization of a GEDT-defined cost function. Application Limitations and Methodological Cautions: The present work is definitional in purpose and not substitutive. As explicitly stated in the text: The manuscript introduces no new biochemical mechanisms and presents no new experimental biological data. The framework does not propose an alternative to thermodynamics, kinetics, or structural biology; rather, it operates at a different descriptive level, focusing on the allocation of the informational burden required to determine a global configuration. The quantification of the biological residue and additional information strictly depends on the adopted model boundaries. The objective is to provide a falsifiable informational language to outline a program for future quantitative verification

Zenodo (CERN European Organization for Nuclear Research)
Hemoglobin structure and function
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Protein folding as a configurational reconstruction: Bio-epistemic application of the General Epistemic Dispersion Theory to adult human hemoglobin — Massimo Comitato · Zenodo (CERN European Organization for Nuclear Research) (2026) | TGRS Research Map | TGRS