A fundamental protein property, thermodynamic stability, revealed solely from large-scale measurements of protein function

By Carlos L. Araya, Douglas M. Fowler, Wentao Chen, I. Muniez, J. Kelly, Stanley Fields. 2012

245 citations recorded by the source corpus.

Subfields: Materials Chemistry, Molecular Biology

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Citations in the corpus

Evolutionary context-integrated deep sequence modeling for protein engineering (2020, methodology): “We collected the fitness measurements of both single and double mutants of six proteins from previous DMS studies [37,49–53] .”
Deep mutational scanning of an RRM domain of the Saccharomyces cerevisiae poly(A)-binding protein (2013, methodology): “We used a product interaction model previously applied to large-scale mutational data (Fowler et al. 2010; Araya et al. 2012) such that in the absence of epistasis, the observed enrichment score of the double mutant should equal the product of the two single mutants’ enrichment scores.”
The genetic landscape of a physical interaction (2018, background): “Thus, as observed in other systems (Araya et al., 2012; Olson et al., 2014), genetic interactions make an important contribution to the outcome of double mutations.”
Pervasive pairwise intragenic epistasis among sequential mutations in TEM-1 β-lactamase (2019, methodology): “calculated epistasis for ~5000 variants in a 34amino acid WW binding domain using phage display [17].”
Systematic exploration of ubiquitin sequence, E1 activation efficiency, and experimental fitness in yeast (2014, background): “While a wealth of studies demonstrate that the fitness effects of mutations are mediated by biochemical changes 19; 20; 21; 22; 23; 24; 25 , most systematic studies of mutants have focused predominantly on either growth effects 14; 26; 27 or biochemical effects 11; 28; 29; 30 .”
Dissecting enzyme function with microfluidic-based deep mutational scanning (2015, background): “An alternative approach for identifying stabilizing mutations from high-throughput sequence–function data was recently developed that involved scoring a residue’s ability to rescue the deleterious effects of other mutations (27).”
Measuring the activity of protein variants on a large scale using deep mutational scanning (2014, background): “Enrich can be adapted to deal with more complex experimental designs, including those that take advantage of subassembly 23 or that incorporate multiple time points 33 .”