Experimental illumination of a fitness landscape

By Ryan T. Hietpas, J. Jensen, Daniel N. A. Bolon. 2011

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Citations in the corpus

Deep mutational scanning of an RRM domain of the Saccharomyces cerevisiae poly(A)-binding protein (2013, methodology): “The deep mutational scanning approach has been used to study the in vivo effect of all possible 171 single amino acid substitutions across a 9-amino acid-long stretch of the yeast Hsp90 (Hietpas et al. 2011) and many of the possible 1425 single amino acid substitutions in the 75-amino acid-long ubiq”
Adaptation in protein fitness landscapes is facilitated by indirect paths (2016, background): “The pairwise epistatic values among other sites (all but 39, 40, 41, and 54) are ranked and represented by the black line.”
A fundamental protein property, thermodynamic stability, revealed solely from large-scale measurements of protein function (2012, unknown): “ε ab 1⁄4 Wab −minðWa;WbÞ; and [3]”
Systematic Mapping of Protein Mutational Space by Prolonged Drift Reveals the Deleterious Effects of Seemingly Neutral Mutations (2015, background): “For example, positions that are 75–90% conserved in Hsp90 tolerated a range of amino acids some of which are not seen in any ortholog [25].”
Enrich: software for analysis of protein function by enrichment and depletion of variants (2011, methodology): “Availability and Implementation: Enrich is implemented in Python and is available under a FreeBSD license at http://depts .washington.edu/sfields/software/enrich/.”
The Evolution of Two-Component Signal Transduction Systems (2012, background): “Most of what is known about kinase-regulator interactions comes from limited alanine-scanning or targeted mutagenesis (10, 79); the application of new, systematic mutagenesis techniques (32) promises to shed significant new light on the specificity and evolution of phosphotransfer in two-component s”
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 .”
Quantifying and understanding the fitness effects of protein mutations: Laboratory versus nature (2016, background): “Indeed, the resolution limit of experimental mappings continues to improve, and many experiments have identified mutations that are adaptive to specific environmental conditions.(28,29) In addition, by performing mutational mappings of both protein fitness and organism fitness, links between biochem”
A rapid, efficient, and economical inverse polymerase chain reaction-based method for generating a site saturation mutant library. (2014, unknown): “Large-scale saturation mutagenesis studies involving single replacements of an amino acid have been carried out previously on a few proteins such as bacteriophage T4 lysozyme [11], lac repressor [12], CfNT2 [13] CcdB [10], HSP90 [14], influenza inhibitor [15], PDZ domain [16], TEM-1 b-lactamase [17]”