Frequencies of amino acid strings in globular protein sequences indicate suppression of blocks of consecutive hydrophobic residues

Protein Sci. 2001 May;10(5):1023-31. doi: 10.1110/ps.33201.


Patterns of hydrophobic and hydrophilic residues play a major role in protein folding and function. Long, predominantly hydrophobic strings of 20-22 amino acids each are associated with transmembrane helices and have been used to identify such sequences. Much less attention has been paid to hydrophobic sequences within globular proteins. In prior work on computer simulations of the competition between on-pathway folding and off-pathway aggregate formation, we found that long sequences of consecutive hydrophobic residues promoted aggregation within the model, even controlling for overall hydrophobic content. We report here on an analysis of the frequencies of different lengths of contiguous blocks of hydrophobic residues in a database of amino acid sequences of proteins of known structure. Sequences of three or more consecutive hydrophobic residues are found to be significantly less common in actual globular proteins than would be predicted if residues were selected independently. The result may reflect selection against long blocks of hydrophobic residues within globular proteins relative to what would be expected if residue hydrophobicities were independent of those of nearby residues in the sequence.

Publication types

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

MeSH terms

  • Alkyl and Aryl Transferases / chemistry
  • Alkyl and Aryl Transferases / metabolism
  • Amino Acids / analysis
  • Amino Acids / chemistry
  • Amino Acids / metabolism*
  • Animals
  • Caenorhabditis elegans
  • Computational Biology*
  • Computer Simulation
  • Cytidine Deaminase / chemistry
  • Cytidine Deaminase / metabolism
  • Databases as Topic
  • Escherichia coli
  • Geranyltranstransferase
  • Lipase / chemistry
  • Lipase / metabolism
  • Models, Molecular
  • Oxidoreductases Acting on CH-NH Group Donors / chemistry
  • Oxidoreductases Acting on CH-NH Group Donors / metabolism
  • Plant Proteins*
  • Probability
  • Protein Conformation
  • Protein Folding*
  • Proteins / chemistry*
  • Proteins / metabolism*
  • Saccharomyces cerevisiae
  • UDPglucose-Hexose-1-Phosphate Uridylyltransferase / chemistry
  • UDPglucose-Hexose-1-Phosphate Uridylyltransferase / metabolism


  • Amino Acids
  • Plant Proteins
  • Proteins
  • phaseolin protein, Phaseolus vulgaris
  • methylamine dehydrogenase
  • Oxidoreductases Acting on CH-NH Group Donors
  • Alkyl and Aryl Transferases
  • Geranyltranstransferase
  • UDPglucose-Hexose-1-Phosphate Uridylyltransferase
  • Lipase
  • Cytidine Deaminase