Amino acid substitutions preserve protein folding by conserving steric and hydrophobicity properties

Istvan Ladunga, Randall F. Smith

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


We present a comprehensive analysis of amino acid substitution patterns (sets of residues in a position of a multiple alignment) and conservation of physicochemical properties in alignments of protein sequences. Of the one million possible substitution patterns, only a few hundred account for the majority of aligned positions. Very similar distributions of substitution patterns are observed in all but one of the diverse databases of multiple alignments. In these substitution patterns we analyzed the conservation of 511 physicochemical and steric amino acid properties. Highest conservation was observed in those steric and transfer free energy-related properties that are crucial for folding. The best conserved steric properties include the minimal width of the side chains and their interactions with other residues. Among the hydrophobicity-related properties, charge and those properties that provide information on propensities to form secondary structures or side chain conformation, appear to be better conserved than pure hydrophobicity measures. Physicochemical sequence analysis based on the most conserved properties is expected to aid searching a protein sequence query against a database of multiple alignments, prediction of secondary and tertiary structures and protein engineering.

Original languageEnglish (US)
Pages (from-to)187-196
Number of pages10
JournalProtein Engineering
Issue number3
StatePublished - Mar 1997


  • Amino acid properties
  • Amino acid substitution
  • Hydrophobicity
  • Multiple alignment
  • Protein folding

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology


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