New insight into long-range nonadditivity within protein double-mutant cycles.

ABSTRACT: Additivity principles in chemistry, biochemistry, and biophysics have been used extensively for decades. Nevertheless, it is well known that additivity frequently breaks down in complex biomacromolecules. Nonadditivity within protein double mutant free energy cycles of spatially close residue pairs is a generally well-understood phenomenon, whereas a robust description of nonadditivity extending over large distances remains to be developed. Here, we test the hypothesis that the mutational effects tend to be nonadditive if two structurally well-separated mutated residues belong to the same rigid cluster within the wild type protein, and additive if they are located within different clusters. We find the hypothesis to be statistically significant with P-values that range from 10(-5) to 10(-6

SUBMITTER: Istomin AY 

PROVIDER: S-EPMC4667956 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature