bi8b00948_si_001.xlsx (12.99 kB)
Experimental Evaluation of Coevolution in a Self-Assembling Particle
dataset
posted on 2018-11-12, 00:00 authored by Emily
C. Hartman, Marco J. Lobba, Andrew H. Favor, Stephanie A. Robinson, Matthew B. Francis, Danielle Tullman-ErcekProtein
evolution occurs via restricted evolutionary paths that
are influenced by both previous and subsequent mutations. This effect,
termed epistasis, is critical in population genetics, drug resistance,
and immune escape; however, the effect of epistasis on the level of
protein fitness is less well characterized. We generated and characterized
a 6615-member library of all two-amino acid combinations in a highly
mutable loop of a virus-like particle. This particle is a model of
protein self-assembly and a promising vehicle for drug delivery and
imaging. In addition to characterizing the effect of all double mutants
on assembly, thermostability, and acid stability, we observed many
instances of epistasis, in which combinations of mutations are either
more deleterious or more beneficial than expected. These results were
used to generate rules governing the effects of multiple mutations
on the self-assembly of the virus-like particle.