A method to identify protein sequences that fold into a known three-dimensional structure

Science. 1991 Jul 12;253(5016):164-70. doi: 10.1126/science.1853201.


The inverse protein folding problem, the problem of finding which amino acid sequences fold into a known three-dimensional (3D) structure, can be effectively attacked by finding sequences that are most compatible with the environments of the residues in the 3D structure. The environments are described by: (i) the area of the residue buried in the protein and inaccessible to solvent; (ii) the fraction of side-chain area that is covered by polar atoms (O and N); and (iii) the local secondary structure. Examples of this 3D profile method are presented for four families of proteins: the globins, cyclic AMP (adenosine 3',5'-monophosphate) receptor-like proteins, the periplasmic binding proteins, and the actins. This method is able to detect the structural similarity of the actins and 70- kilodalton heat shock proteins, even though these protein families share no detectable sequence similarity.

Publication types

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

MeSH terms

  • Actins / chemistry
  • Actins / ultrastructure
  • Algorithms
  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / chemistry
  • Escherichia coli Proteins*
  • Molecular Structure
  • Myoglobin / chemistry
  • Myoglobin / ultrastructure
  • Periplasmic Binding Proteins*
  • Protein Conformation*
  • Proteins / chemistry*
  • Receptors, Cyclic AMP / chemistry
  • Receptors, Cyclic AMP / ultrastructure
  • Structure-Activity Relationship


  • Actins
  • Carrier Proteins
  • Escherichia coli Proteins
  • Myoglobin
  • Periplasmic Binding Proteins
  • Proteins
  • RbsB protein, E coli
  • Receptors, Cyclic AMP