期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2018
卷号：115
期号：20
页码：E4559-E4568
DOI：10.1073/pnas.1716215115
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
关键词：protein evolution ; epistasis ; genotype-to-phenotype map ; Green function ; dimensional reduction
