Identification of amino acids involved in protein structural uniqueness: implication for de novo protein design

• Published in: Protein engineering Vol. 15; no. 7; pp. 555 - 560
• Main Authors: Isogai, Yasuhiro, Ota, Motonori, Ishii, Anna, Ishida, Manabu, Nishikawa, Ken
• Format: Journal Article
• Language: English
• Published: England Oxford Publishing Limited (England) 01.07.2002
• Subjects: Amino Acid Sequence; Amino Acids - chemistry; Computational Biology - methods; Molecular Conformation; Molecular Sequence Data; Protein Engineering; Protein Folding; Protein Structure, Secondary; Protein Structure, Tertiary; Proteins - chemical synthesis; Proteins - chemistry; Thermodynamics
• ISSN: 0269-2139; 1741-0126; 1741-0134
• DOI: 10.1093/protein/15.7.555

Structural uniqueness is characteristic of native proteins and is essential to express their biological functions. The major factors that bring about the uniqueness are specific interactions between hydrophobic residues and their unique packing in the protein core. To find the origin of the uniqueness in their amino acid sequences, we analyzed the distribution of the side chain rotational isomers (rotamers) of hydrophobic amino acids in protein tertiary structures and derived deltaS(contact), the conformational-entropy changes of side chains by residue-residue contacts in each secondary structure. The deltaS(contact) values indicate distinct tendencies of the residue pairs to restrict side chain conformation by inter-residue contacts. Of the hydrophobic residues in alpha-helices, aliphatic residues (Leu, Val, Ile) strongly restrict the side chain conformations of each other. In beta-sheets, Met is most strongly restricted by contact with Ile, whereas Leu, Val and Ile are less affected by other residues in contact than those in alpha-helices. In designed and native protein variants, deltaS(contact) was found to correlate with the folding-unfolding cooperativity. Thus, it can be used as a specificity parameter for designing artificial proteins with a unique structure.