Page 163 - Academic Press Encyclopedia of Physical Science and Technology 3rd BioChemistry

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Encyclopedia of Physical Science and Technology EN013D-616 July 27, 2001 12:5

Protein Structure 203

i+3 i+2
i+3
i+2

i+1
i+1
i
i

Type I turn Type II turn
(a) (b)

i+3
i+2

i+1

i

Type III turn
(c)
FIGURE 8 Types I, II, and III turns.

Protein stability is determined by an enormous number in terms of their thermodynamic properties. Much of what
of weak interactions observed in the folded state which is known about the hydrophobic effect has been derived
have to be balanced against an almost equivalent set of from studying the transfer of hydrocarbons from the liquid
interactions with water in the unfolded state. This is a phase into water; indeed the thermodynamics of protein
complex problem since every amino acid residue has po- folding closely follow the behavior of simple hydrophobic
tential for polar interactions via the peptide bond and a molecules in water.
variety of ionic, polar, and nonpolar interactions through Studies of hydrocarbon models demonstrate that at
its side chains. This accounts for the difficulty in predict- room temperature the insolubility of hydrophobic com-
ing structure directly from its amino acid sequence since pounds is dominated by entropic rather than enthalpic
the errors in any energy computation are far larger than considerations. This is often explained as a water-ordering
the net stability of the protein. effect where the insertion of a hydrophobic molecule into
an aqueous environment induces a diffusely ordered wa-
ter shell surrounding the molecule, akin to the formation
A. Hydrophobic Effect
of clathrates around noble gases and simple hydrocar-
The major driving force in protein folding is the hydropho- bons.Thisshellformsbecausethehydrophobiccompound
bic effect. This is the tendency for hydrophobic molecules cannot form hydrogen bonds to the water that surrounds
to isolate themselves from contact with water. As a conse- it. Consequently those water molecules have a more re-
quence during protein folding the hydrophobic side chains stricted set of neighbors with whom to fulfil their hydrogen
become buried in the interior of the protein. The ex- bonding capacities. This reduces their degrees of rota-
act physical explanation of the behavior of hydrophobic tional freedom and thus leads to a reduction in entropy.
molecules in water is complex and can best be described This simple explanation based on ordering of water is