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Stabilizing nonpolar/polar side‐chain interactions in the α‐helix
Author(s) -
Andrew Charles D.,
Penel Simon,
Jones Gareth R.,
Doig Andrew J.
Publication year - 2001
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.1161
Subject(s) - polar , helix (gastropod) , chemistry , side chain , circular dichroism , alpha helix , polarity (international relations) , stereochemistry , crystallography , alkyl , amino acid , hydrophobic effect , protein structure , polymer , organic chemistry , biochemistry , biology , ecology , physics , astronomy , snail , cell
A simplistic, yet often used, view of protein stability is that amino acids attract other amino acids with similar polarity, whereas nonpolar and polar side chains repel. Here we show that nonpolar/polar interactions, namely Val or Ile bonding to Lys or Arg in α‐helices, can in fact be stabilizing. Residues spaced i, i + 4 in α‐helices are on the same face of the helix, with potential to favorably interact and stabilize the structure. We observe that the nonpolar/polar pairs Ile‐Lys, Ile‐Arg, and Val‐Lys occur in protein helices more often than expected when spaced i, i + 4. Partially helical peptides containing pairs of nonpolar/polar residues were synthesized. Controls with i, i + 5 spacing have the residues on opposite faces of the helix and are less helical than the test peptides with the i, i + 4 interactions. Experimental circular dichroism results were analyzed with helix‐coil theory to calculate the free energy for the interactions. All three stabilize the helix with Δ G between −0.14 and −0.32 kcal · mol −1 . The interactions are hydrophobic with contacts between Val or Ile and the alkyl groups in Arg or Lys. Side chains such as Lys and Arg can thus interact favorably with both polar and nonpolar residues. Proteins 2001;45:449–455. © 2001 Wiley‐Liss, Inc.