Double Mutant Cycles as a Tool to Address Folding, Binding, and Allostery

Double Mutant Cycles as a Tool to Address Folding, Binding, and Allostery

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...

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Main Authors: Livia Pagano, Angelo Toto, Francesca Malagrinò, Lorenzo Visconti, Per Jemth, Stefano Gianni
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:International Journal of Molecular Sciences
Subjects:
coupling energy
site-directed mutagenesis
interaction networks
Online Access:https://www.mdpi.com/1422-0067/22/2/828
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spelling doaj-51727ef8285c4d60a4c0bca37a9c6dda2021-01-16T00:04:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-012282882810.3390/ijms22020828Double Mutant Cycles as a Tool to Address Folding, Binding, and AllosteryLivia Pagano0Angelo Toto1Francesca Malagrinò2Lorenzo Visconti3Per Jemth4Stefano Gianni5Istituto 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, ItalyIstituto 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, ItalyIstituto 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, ItalyIstituto 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, ItalyDepartment of Medical Biochemistry and Microbiology, Uppsala University, SE-75123 Uppsala, SwedenIstituto 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, ItalyQuantitative 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.https://www.mdpi.com/1422-0067/22/2/828coupling energysite-directed mutagenesisinteraction networks
collection DOAJ
language English
format Article
sources DOAJ
author Livia Pagano
Angelo Toto
Francesca Malagrinò
Lorenzo Visconti
Per Jemth
Stefano Gianni
spellingShingle Livia Pagano
Angelo Toto
Francesca Malagrinò
Lorenzo Visconti
Per Jemth
Stefano Gianni
Double Mutant Cycles as a Tool to Address Folding, Binding, and Allostery
International Journal of Molecular Sciences
coupling energy
site-directed mutagenesis
interaction networks
author_facet Livia Pagano
Angelo Toto
Francesca Malagrinò
Lorenzo Visconti
Per Jemth
Stefano Gianni
author_sort Livia Pagano
title Double Mutant Cycles as a Tool to Address Folding, Binding, and Allostery
title_short Double Mutant Cycles as a Tool to Address Folding, Binding, and Allostery
title_full Double Mutant Cycles as a Tool to Address Folding, Binding, and Allostery
title_fullStr Double Mutant Cycles as a Tool to Address Folding, Binding, and Allostery
title_full_unstemmed Double Mutant Cycles as a Tool to Address Folding, Binding, and Allostery
title_sort double mutant cycles as a tool to address folding, binding, and allostery
publisher MDPI AG
series International Journal of Molecular Sciences
issn 1661-6596
1422-0067
publishDate 2021-01-01
description 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.
topic coupling energy
site-directed mutagenesis
interaction networks
url https://www.mdpi.com/1422-0067/22/2/828
work_keys_str_mv AT liviapagano doublemutantcyclesasatooltoaddressfoldingbindingandallostery
AT angelototo doublemutantcyclesasatooltoaddressfoldingbindingandallostery
AT francescamalagrino doublemutantcyclesasatooltoaddressfoldingbindingandallostery
AT lorenzovisconti doublemutantcyclesasatooltoaddressfoldingbindingandallostery
AT perjemth doublemutantcyclesasatooltoaddressfoldingbindingandallostery
AT stefanogianni doublemutantcyclesasatooltoaddressfoldingbindingandallostery
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