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.

Hint approach on Transthyretin folding/unfolding mechanism comprehension / Agosta, Federica; Cozzini, Pietro. - In: COMPUTERS IN BIOLOGY AND MEDICINE. - ISSN 0010-4825. - 155:(2023), p. 106667. [10.1016/j.compbiomed.2023.106667]

Hint approach on Transthyretin folding/unfolding mechanism comprehension

Agosta, Federica;Cozzini, Pietro
2023-01-01

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.
2023
Hint approach on Transthyretin folding/unfolding mechanism comprehension / Agosta, Federica; Cozzini, Pietro. - In: COMPUTERS IN BIOLOGY AND MEDICINE. - ISSN 0010-4825. - 155:(2023), p. 106667. [10.1016/j.compbiomed.2023.106667]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2953093
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