Epistasis in protein evolution

TN Starr, JW Thornton - Protein science, 2016 - Wiley Online Library
The structure, function, and evolution of proteins depend on physical and genetic
interactions among amino acids. Recent studies have used new strategies to explore the …

Evolutionary mechanisms shaping the maintenance of antibiotic resistance

P Durão, R Balbontín, I Gordo - Trends in microbiology, 2018 - cell.com
Antibiotics target essential cellular functions but bacteria can become resistant by acquiring
either exogenous resistance genes or chromosomal mutations. Resistance mutations …

Expanding functional protein sequence spaces using generative adversarial networks

D Repecka, V Jauniskis, L Karpus… - Nature Machine …, 2021 - nature.com
De novo protein design for catalysis of any desired chemical reaction is a long-standing goal
in protein engineering because of the broad spectrum of technological, scientific and …

Informed training set design enables efficient machine learning-assisted directed protein evolution

BJ Wittmann, Y Yue, FH Arnold - Cell systems, 2021 - cell.com
Directed evolution of proteins often involves a greedy optimization in which the mutation in
the highest-fitness variant identified in each round of single-site mutagenesis is fixed. The …

Cell-wide analysis of protein thermal unfolding reveals determinants of thermostability

P Leuenberger, S Ganscha, A Kahraman, V Cappelletti… - Science, 2017 - science.org
INTRODUCTION Temperature is crucially important to life. Small temperature changes can
differentiate optimal and lethal growth conditions of living organisms. Because of the higher …

Exploring protein fitness landscapes by directed evolution

PA Romero, FH Arnold - Nature reviews Molecular cell biology, 2009 - nature.com
Directed evolution circumvents our profound ignorance of how a protein's sequence
encodes its function by using iterative rounds of random mutation and artificial selection to …

Causes of molecular convergence and parallelism in protein evolution

JF Storz - Nature Reviews Genetics, 2016 - nature.com
To what extent is the convergent evolution of protein function attributable to convergent or
parallel changes at the amino acid level? The mutations that contribute to adaptive protein …

A comprehensive biophysical description of pairwise epistasis throughout an entire protein domain

CA Olson, NC Wu, R Sun - Current biology, 2014 - cell.com
Background Nonadditivity in fitness effects from two or more mutations, termed epistasis, can
result in compensation of deleterious mutations or negation of beneficial mutations. Recent …

Stability effects of mutations and protein evolvability

N Tokuriki, DS Tawfik - Current opinion in structural biology, 2009 - Elsevier
The past several years have seen novel insights at the interface of protein biophysics and
evolution. The accepted paradigm that proteins can tolerate nearly any amino acid …

[HTML][HTML] Evolvability as a function of purifying selection in TEM-1 β-lactamase

MA Stiffler, DR Hekstra, R Ranganathan - Cell, 2015 - cell.com
Evolvability—the capacity to generate beneficial heritable variation—is a central property of
biological systems. However, its origins and modulation by environmental factors have not …