An approach to energy compensation
DOI:
https://doi.org/10.62059/w2jn3a04Keywords:
Compensatory mutations, Structural coupling, Intramolecular epistasisAbstract
Intramolecular epistasis, in the context of energy compensation, describes how pairs of residues within a protein interact to preserve structural stability under perturbations. This work presents a mathematical framework derived from thermodynamic principles to formalize energy compensation between residues. By defining the scalar function Cpq and incorporating first- and second-order derivatives, local and cross curvatures, and sensitivity coefficients, the model captures how perturbations in conformational states propagate through the protein network. The Hessian matrix is introduced to characterize energetic rigidity, flexibility, and structural coupling, while the coefficients λpq quantify the efficiency of energy transmission and reveal conditions of robustness, plasticity, independence, conflict, and destructive resonance. Altogether, this approach provides a conceptual and quantitative basis for mapping the energetic geometry of proteins, identifying critical regions that act as buffers, absorbers, or amplifiers of perturbations, and advancing the understanding of how proteins maintain homeostasis and adaptive stability.
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Copyright (c) 2026 Maurizio Cavani (Autor/a)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This preprint contains the reported license and associated copyright. Once published in an associated journal or other publisher, the published version assumes the publisher's terms and conditions.
