Chapter 4

thermodynamically the most stable — that is, having the lowest free energy (G).

Proteins in any of their functional, folded conformations are often called native proteins

critical to function. However, in many cases, parts of proteins lack discernible structure. These protein segments are intrinsically disordered. In some cases, entire proteins are intrinsically disordered, yet are fully functional.

Stability is the tendency of a protein to maintain a native conformation. Native proteins are only marginally stable; the ΔG separating the folded and unfolded states in typical proteins under physiological conditions is in the range of only 5 to 65 kJ/mol.

either stabilizing or destabilizing. We must therefore look elsewhere to understand why a particular native conformation is favored

the hydrophobic effect generally predominates. Pure water contains a network of hydrogen-bonded H2O molecules. No other molecule has the hydrogen-bonding potential of water, and the presence of other molecules in an aqueous solution disrupts the hydrogen bonding of water

, the optimal arrangement of hydrogen bonds results in a highly structured shell, or solvation layer, of water around the molecule (see Fig. 2-7). The increased order of the water molecules in the solvation layer correlates with an unfavorable decrease in the entropy of the water.

can thus provide significant stabilization to a protein structure. This trend explains the increased occurrence of buried salt bridges in the proteins of thermophilic organisms. Ionic interactions also limit structural flexibility and confer a uniqueness to a particular protein structure that the clustering of nonpolar groups via the hydrophobic effect cannot provide.

(also known as torsion angles) called ϕ (phi), ψ (psi), and ω (omega), reflecting rotation about each of the three repeating bonds in the peptide backbone.

the angle at the intersection of two planes.

Two successive bond vectors describe a plane. Three successive bond vectors describe two planes (the central bond vector is common to both; Fig. 4-2c), and the angle between these two planes is what we measure to describe peptide conformation.

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one or more stable threedimensional conformations that reflect its function. Some proteins have segments that are intrinsically disordered but are nonetheless essential for function

multiple weak, noncovalent interactions and forces

the increase in entropy of the surrounding water when nonpolar molecules or groups are clustered together, makes the major contribution to stabilizing the globular form of most soluble proteins.

thermodynamically most stable structures.

attractive forces between molecular dipoles that occur over short distances. Individually these interactions are weak, but they combine in well-packed protein structures to provide significant effects and stabilization.

n structure. The peptide bond has a partial double-bond character that keeps the entire six-atom peptide group in a rigid planar configuration. The N—Cα and Cα—C bonds can rotate to define the dihedral angles ϕ and ψ, respectively, although permitted values of ϕ and ψ are limited by steric clashes and other constraints

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The term secondary structure refers to any chosen segment of a polypeptide chain and describes the local spatial arrangement of its main-chain atoms, without regard to the positioning of its side chains or its relationship to other segments. A regular secondary structure occurs when each dihedral angle, ϕ and ψ, remains the same or nearly the same throughout the segment

these dihedral angles, and they even vary somewhat within a single, continuous segment so as to produce subtle bends or kinks in the helical axis

(1) the intrinsic propensity of an amino acid residue to form an α helix; (2) the interactions between R groups, particularly those spaced three (or four) residues apart; (3) the bulkiness of adjacent R groups; (4) the occurrence of Pro and Gly residues; and (5) interactions between amino acid residues at the ends of the helical segment and the electric dipole inherent to the α helix.

the identity and sequence of amino acid residues within the segment.