Premium
Effect of the N2 residue on the stability of the α‐helix for all 20 amino acids
Author(s) -
Cochran Duncan A.E.,
Doig Andrew J.
Publication year - 2001
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.50701
Subject(s) - helix (gastropod) , hydrogen bond , chemistry , crystallography , circular dichroism , collagen helix , alpha helix , residue (chemistry) , protein structure , amino acid , stereochemistry , peptide , triple helix , molecule , biochemistry , biology , ecology , organic chemistry , snail
N2 is the second position in the α‐helix. All 20 amino acids were placed in the N2 position of a synthetic helical peptide (CH 3 CO‐[AXAAAAKAAAAKAAGY]‐NH 2 ) and the helix content was measured by circular dichroism spectroscopy at 273K. The dependence of peptide helicity on N2 residue identity has been used to determine a free‐energy scale by analysis with a modified Lifson‐Roig helix‐coil theory that includes a parameter for the N2 energy ( n2 ). The rank order of ΔΔG (relative to Ala) is Glu − , Asp − > Ala > Glu 0 , Leu, Val, Gln, Thr, Ile, Ser, Met, Asp 0 , His 0 , Arg, Cys, Lys, Phe > Asn, > Gly, His + , Pro, Tyr. The results correlate very well with N2 propensities in proteins, moderately well with N1 and helix interior preferences, and not at all with N‐cap preferences. The strongest energetic effects result from interactions with the helix dipole, which favors negative charges at the helix N terminus. Hydrogen bonds to side chains at N2, such as Gln, Ser, and Thr, are weak, despite occurring frequently in protein crystal structures, in contrast to the N‐cap position. This is because N‐cap hydrogen bonds are close to linear, whereas N2 hydrogen bonds have poor geometry. These results can be used to modify protein stability rationally, help design helices, and improve prediction of helix location and stability.