Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Modeling sequence-space exploration and emergence of epistatic signals in protein evolution During their evolution, proteins explore sequence space via an interplay between random mutations and phenotypic selection. Here we build upon recent progress in reconstructing data-driven fitness landscapes for families of homologous proteins, to propose stochastic models of experimental protein evolution. These models predict quantitatively important features of experimentally evolved sequence libraries, like fitness distributions and position-specific mutational spectra. They also allow us to efficiently simulate sequence libraries for a vast array of combinations of experimental parameters like sequence divergence, selection strength and library size. We showcase the potential of the approach in re-analyzing two recent experiments to determine protein structure from signals of epistasis emerging in experimental sequence libraries. To be detectable, these signals require sufficiently large and sufficiently diverged libraries. Our modeling framework offers a quantitative explanation for the variable success of recently published experiments. Furthermore, we can fore-cast the outcome of time- and resource-intensive evolution experiments, opening thereby a way to computationally optimize experimental protocols.
26
The categories of this paper are: biochemistry
5
The categories of this paper are: cell
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The categories of this paper are: behavior
21
The categories of this paper are: toxicology
13
The categories of this paper are: animal
30
The categories of this paper are: scientific
8
The categories of this paper are: genomics
28
The categories of this paper are: communication
22
The categories of this paper are: physiology
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The categories of this paper are: biophysics
29
The categories of this paper are: education
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The categories of this paper are: pharmacology
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The categories of this paper are: and
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The categories of this paper are: neuroscience
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The categories of this paper are: plant
1
The categories of this paper are: bioinformatics