Open AccessFolding units in globular proteins.
Author(s) -
Arthur M. Lesk,
George D. Rose
Publication year - 1981
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.78.7.4304
Subject(s) - globular protein , folding (dsp implementation) , protein folding , crystallography , globular cluster , cluster (spacecraft) , biological system , hierarchy , population , chemistry , chain (unit) , chemical physics , monomer , computational biology , computer science , physics , biology , biochemistry , engineering , astrophysics , programming language , demography , organic chemistry , astronomy , galaxy , sociology , economics , electrical engineering , market economy , polymer
We present a method to identify all compact, contiguous-chain, structural units in a globular protein from x-ray coordinates. These units are then used to describe a complete set of hierarchic folding pathways for the molecule. Our analysis shows that the larger units are combinations of smaller units, giving rise to a structural hierarchy ranging from the whole protein monomer through supersecondary structures down to individual helices and strands. It turns out that there is more than one way to assemble the protein by self-association of its compact units. However, the number of possible pathways is small--small enough to be exhaustively explored by a computer program. The hierarchic organization of compact units in protein molecules is consistent with a model for folding by hierarchic condensation. In this model, neighboring hydrophobic chain sites interact to form folding clusters, with further stepwise cluster association giving rise to a population of folding intermediates.