Double-mutant cycles: new directions and applications. (October 2019)

• Record Type: Journal Article
• Authors: Horovitz, Amnon; Fleisher, Rachel C; Mondal, Tridib
• Is Part Of: Current opinion in structural biology. Volume 58(2019)
• Page Start: 10
• Page End: 17
• Publication Date: 2019-10
• Subjects: Molecular biology -- Periodicals; 570
• DOI: 10.1016/j.sbi.2019.03.025
• Languages: English
• ISSNs: 0959-440X

Abstract

Graphical abstract: Highlights: Double-mutant cycles and native mass spectrometry can facilitate docking. High-throughput double-mutant cycle analysis can reveal patterns of epistasis. Multi-dimensional mutant cycles can reveal higher-order coupling and cooperativity. Double-mutant cycles can be used to validate correlated mutation analysis. Abstract : Double-mutant cycle (DMC) analysis is a powerful approach for detecting and quantifying the energetics of both direct and long-range interactions in proteins and other chemical systems. It can also be used to unravel higher-order interactions (e.g. three-body effects) that lead to cooperativity in protein folding and function. In this review, we describe new applications of DMC analysis based on advances in native mass spectrometry and high-throughput methods such as next generation sequencing and protein complementation assays. These developments have facilitated carrying out high-throughput DMC analysis, which can be used to characterize increasingly higher-order interactions and very large interaction networks in proteins. Such studies have provided insights into the extent of cooperativity (epistasis) in protein structures. High-throughput DMC studies have also been used to validate correlated mutation analysis and can provide restraints for protein docking.