54 1 Amino Acids, Peptides, Proteins
occur only; (2)β-structures occur only; (3)α-
helical andβ-structural portions occur in separate
segments on the peptide chain; (4)α-helix and
β-structures alternate along the peptide chain; and
(5)α-helix andβ-structures do not exist.
The process of peptide chain folding is not yet
fully understood. It begins spontaneously, proba-
bly arising from one center or from several cen-
ters of high stability in larger proteins. The ten-
dency to form regular structural elements shows
a very different development in the various amino
acid residues. Table 1.24 lists data which were
derived from the analysis of globular proteins of
known conformation. The data indicate, for ex-
ample, that Met, Glu, Leu and Ala are strongly
helix-forming. Gly and Pro on the other hand
show a strong helix-breaking tendency. Val, Ile
and Leu promote the formation of pleated-sheet
structures, while Asp, Glu and Pro prevent them.
Table 1.24.Normalized frequenciesaof amino acid
residues in the regular structural elements of globular
proteins
Amino acid α-Helix Pleated sheet β-Turn
(Pα)(Pβ)(Pt)
Ala 1. 29 0. 90 0. 78
Cys 1. 11 0. 74 0. 80
Leu 1. 30 1. 02 0. 59
Met 1. 47 0. 97 0. 39
Glu 1. 44 0. 75 1. 00
Gln 1. 27 0. 80 0. 97
His 1. 22 1. 08 0. 69
Lys 1. 23 0. 77 0. 96
Val 0. 91 1. 49 0. 47
Ile 0. 97 1. 45 0. 51
Phe 1. 07 1. 32 0. 58
Tyr 0. 72 1. 25 1. 05
Trp 0. 99 1. 14 0. 75
Thr 0. 82 1. 21 1. 03
Gly 0. 56 0. 92 1. 64
Ser 0. 82 0. 95 1. 33
Asp 1. 04 0. 72 1. 41
Asn 0. 90 0. 76 1. 28
Pro 0. 52 0. 64 1. 91
Arg 0. 96 0. 99 0. 88
aShown is the fraction of an amino acid in a regular
structural element, related to the fraction of all amino
acids of the same structural element. P=1 means ran-
dom distribution; P>1 means enrichment, P<1 means
depletion. The data are based on an analysis of 66 pro-
tein structures.
Pro and Gly are important building blocks of
turns. Arginine does not prefer any of the three
structures. By means of such data it is possible to
forecast the expected conformations for a given
amino acid sequence.
Folding of the peptide chain packs it densely
by formation of a large number of intermolecu-
lar noncovalent bonds. Data on the nature of the
bonds involved are provided in Table 1.25.
The H-bonds formed between main chains, main
and side chains and side-side chains are of par-
ticular importance for folding. The portion of po-
lar groups involved in H-bond buildup in proteins
of Mr> 8 .9 kdal appears to be fairly constant at
about 50%.
The hydrophobic interaction of the nonpolar re-
gions of the peptide chains also plays an import-
ant role in protein folding. These interactions are
responsible for the fact that nonpolar groups are
folded to a great extent towards the interior of the
protein globule. The surface areas accessible to
water molecules have been calculated for both un-
folded and native folded forms for a number of
monomeric proteins with known conformations.
The proportion of the accessible surface in the
stretched state, which tends to be burried in the in-
terior of the globule as a result of folding, is a sim-
ple linear function of the molecular weight (M).
The gain in free energy for the folded surface isTable 1.25.Bond-types in proteinsType Examples Bond
strength
(kJ/mole)Covalent –S–S– ca.− 230
bonds
Electrostatic−COO–H 3 N+−− 21
bonds >C=O O=C< + 1. 3
Hydrogen –O–H···O< − 16. 7
bonds >N–H···O=C< − 12. 5Hydrophobic
bonds0. 01 b–Ala···Ala– − 3
–Val···Val– − 8
–Leu···Leu– − 9
–Phe···Phe– − 13
–Trp···Trp– − 19
aForε=4.bPer Å (^2) -surface area.