Proposed mechanism for stability of proteins to evolutionary mutations

Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10682-6. doi: 10.1073/pnas.95.18.10682.

Abstract

It is shown that the sequence-ordering tendencies induced by design into different fast-folding, thermally stable native structures interfere. This interference results in a type of quasiorthogonality between optimal native structures, which divides sequence space into fast-folding, thermally stable families surrounded by slow-folding, low stability shells. A concrete example of this effect is provided by using a simple alpha carbon type model in which a complete correspondence is established between sequence and structure. It is speculated that gaps can occur in the space of protein-like sequences separating the sequence families and resulting in a mechanism for stability and diversity of protein sequence information.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Evolution, Molecular*
  • Hydrogen Bonding
  • Models, Chemical
  • Mutation*
  • Protein Folding
  • Proteins / chemistry*
  • Proteins / genetics

Substances

  • Proteins