SEARCH

SEARCH BY CITATION

Keywords:

  • protein design;
  • negative design;
  • small-molecule binding;
  • monomer design;
  • Rossman fold design;
  • aromatic residues;
  • Boltzmann distribution;
  • entropy of binding

Abstract

Protein-design methodology can now generate models of protein structures and interfaces with computed energies in the range of those of naturally occurring structures. Comparison of the properties of native structures and complexes to isoenergetic design models can provide insight into the properties of the former that reflect selection pressure for factors beyond the energy of the native state. We report here that sidechains in native structures and interfaces are significantly more constrained than designed interfaces and structures with equal computed binding energy or stability, which may reflect selection against potentially deleterious non-native interactions.