Scaling properties of evolutionary paths in a biophysical model of protein adaptation

Phys Biol. 2015 May 28;12(4):045001. doi: 10.1088/1478-3975/12/4/045001.

Abstract

The enormous size and complexity of genotypic sequence space frequently requires consideration of coarse-grained sequences in empirical models. We develop scaling relations to quantify the effect of this coarse-graining on properties of fitness landscapes and evolutionary paths. We first consider evolution on a simple Mount Fuji fitness landscape, focusing on how the length and predictability of evolutionary paths scale with the coarse-grained sequence length and alphabet. We obtain simple scaling relations for both the weak- and strong-selection limits, with a non-trivial crossover regime at intermediate selection strengths. We apply these results to evolution on a biophysical fitness landscape that describes how proteins evolve new binding interactions while maintaining their folding stability. We combine the scaling relations with numerical calculations for coarse-grained protein sequences to obtain quantitative properties of the model for realistic binding interfaces and a full amino acid alphabet.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence*
  • Biophysical Phenomena
  • Evolution, Molecular*
  • Models, Genetic*
  • Proteins / chemistry*

Substances

  • Proteins