Green function of correlated genes in a minimal mechanical model of protein evolution.

Citation data:

Proceedings of the National Academy of Sciences of the United States of America, ISSN: 1091-6490, Vol: 115, Issue: 20, Page: E4559-E4568

Publication Year:
2018
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arXiv Id:
1801.03681
PMID:
29712824
DOI:
10.1073/pnas.1716215115
Repository URL:
http://scholarworks.unist.ac.kr/handle/201301/24167
Author(s):
Dutta, Sandipan; Eckmann, Jean-Pierre; Libchaber, Albert; Tlusty, Tsvi
Publisher(s):
NATL ACAD SCIENCES
Tags:
Multidisciplinary; protein evolution; epistasis; genotype-to-phenotype map; Green function; dimensional reduction
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article description
The function of proteins arises from cooperative interactions and rearrangements of their amino acids, which exhibit large-scale dynamical modes. Long-range correlations have also been revealed in protein sequences, and this has motivated the search for physical links between the observed genetic and dynamic cooperativity. We outline here a simplified theory of protein, which relates sequence correlations to physical interactions and to the emergence of mechanical function. Our protein is modeled as a strongly coupled amino acid network with interactions and motions that are captured by the mechanical propagator, the Green function. The propagator describes how the gene determines the connectivity of the amino acids and thereby, the transmission of forces. Mutations introduce localized perturbations to the propagator that scatter the force field. The emergence of function is manifested by a topological transition when a band of such perturbations divides the protein into subdomains. We find that epistasis-the interaction among mutations in the gene-is related to the nonlinearity of the Green function, which can be interpreted as a sum over multiple scattering paths. We apply this mechanical framework to simulations of protein evolution and observe long-range epistasis, which facilitates collective functional modes.