The CHAIN program: forging evolutionary links to underlying mechanisms

Trends Biochem Sci. 2007 Nov;32(11):487-93. doi: 10.1016/j.tibs.2007.08.009. Epub 2007 Oct 24.

Abstract

Proteins evolve new functions by modifying and extending the molecular machinery of an ancestral protein. Such changes show up as divergent sequence patterns, which are conserved in descendent proteins that maintain the divergent function. After multiply-aligning a set of input sequences, the CHAIN program partitions the sequences into two functionally divergent groups and then outputs an alignment that is annotated to reveal the selective pressures imposed on divergent residue positions. If atomic coordinates are also provided, hydrogen bonds and other atomic interactions associated with various categories of divergent residues are graphically displayed. Such analyses establish links between protein evolutionary divergence and functionally crucial atomic features and, as a result, can suggest plausible molecular mechanisms for experimental testing. This is illustrated here by its application to bacterial clamp-loader ATPases.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine Triphosphatases / chemistry
  • Amino Acid Sequence
  • Biological Evolution*
  • Hydrogen Bonding
  • Molecular Sequence Data
  • Proteins / chemistry
  • Proteins / genetics*
  • Sequence Homology, Amino Acid

Substances

  • Proteins
  • Adenosine Triphosphatases