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Updated: Aug 9, 2025

Analysis of Protein Folding, Transport, and Degradation in Living Cells by Radioactive Pulse Chase
Published on: February 12, 2019
Hint approach on Transthyretin folding/unfolding mechanism comprehension
Federica Agosta1, Pietro Cozzini1
1Molecular Modeling Laboratory, Food and Drug Department, University of Parma, Parco Area delle Scienze 17/A, 43124, Parma, Italy.
Abstract:
Non-covalent intramolecular interactions play a key role in the protein folding process. Aminoacidic mutations or changes in physiological conditions such as pH and/or temperature variations can compromise intramolecular stability generating misfolding or unfolding proteins with consequent impairment of functionality and the triggering of pathological states. The intramolecular HINT scoring function recently implemented and validated, is proposed as a rapid and sensitive method for the evaluation of different conformational states characterizing destabilization processes. In this work, the stability of Transthyretin, whose denaturation is related to amyloid fibril formation, is evaluated by generating multiple structural mutated models under different pH conditions in comparison with experimental data. These results suggest that the HINT scoring function can be used for an accurate and rapid evaluation and computational prediction of the effects of structural changes on any protein system.
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