Double Mutant Cycles as a Tool to Address Folding, Binding, and Allostery
1
Istituto Pasteur—Fondazione Cenci Bolognetti, Dipartimento di Scienze Biochimiche ‘A. Rossi Fanelli’ and Istituto di Biologia e Patologia Molecolari del CNR, Sapienza Università di Roma, 00185 Rome, Italy
2
Department of Medical Biochemistry and Microbiology, Uppsala University, SE-75123 Uppsala, Sweden
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(2), 828; https://doi.org/10.3390/ijms22020828
Received: 31 December 2020 / Revised: 13 January 2021 / Accepted: 13 January 2021 / Published: 15 January 2021
(This article belongs to the Special Issue Protein Folding and Misfolding ---- Structure and Functions)
Quantitative measurement of intramolecular and intermolecular interactions in protein structure is an elusive task, not easy to address experimentally. The phenomenon denoted ‘energetic coupling’ describes short- and long-range interactions between two residues in a protein system. A powerful method to identify and quantitatively characterize long-range interactions and allosteric networks in proteins or protein–ligand complexes is called double-mutant cycles analysis. In this review we describe the thermodynamic principles and basic equations that underlie the double mutant cycle methodology, its fields of application and latest employments, and caveats and pitfalls that the experimentalists must consider. In particular, we show how double mutant cycles can be a powerful tool to investigate allosteric mechanisms in protein binding reactions as well as elusive states in protein folding pathways.
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MDPI and ACS Style
Pagano, L.; Toto, A.; Malagrinò, F.; Visconti, L.; Jemth, P.; Gianni, S. Double Mutant Cycles as a Tool to Address Folding, Binding, and Allostery. Int. J. Mol. Sci. 2021, 22, 828. https://doi.org/10.3390/ijms22020828
AMA Style
Pagano L, Toto A, Malagrinò F, Visconti L, Jemth P, Gianni S. Double Mutant Cycles as a Tool to Address Folding, Binding, and Allostery. International Journal of Molecular Sciences. 2021; 22(2):828. https://doi.org/10.3390/ijms22020828
Chicago/Turabian StylePagano, Livia; Toto, Angelo; Malagrinò, Francesca; Visconti, Lorenzo; Jemth, Per; Gianni, Stefano. 2021. "Double Mutant Cycles as a Tool to Address Folding, Binding, and Allostery" Int. J. Mol. Sci. 22, no. 2: 828. https://doi.org/10.3390/ijms22020828
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