| | | | | Cantor, C.R.; Schimmel, P.R.Biophysical Chemistry, Part I and Part III. New York: W.H. Freeman, 1980.
Eisenberg, D.; Crothers, D.Physical Chemistry with Applications to the Life Sciences. Menlo Park, CA: Benjamin-Cummings, 1979.
Pauling, L.The Nature of the Chemical Bond, 3rd ed. Ithaca, NY: Cornell University Press, 1960.
Whitesides, G.M.; Mathias, J.P.; Seto, C.T.Molecular self-assembly and nanochemistry: a chemical strategy for the synthesis of nanostructures. Science 254:1312-1319, 1991 [PubMed] |
|
| | Abeles, R.H.; Frey, P.A.; Jencks, W.P.Biochemistry. Boston: Jones and Bartlett, 1992.
Burley, S.K.; Petsko, G.A.Weakly polar interactions in proteins. Adv. Prot. Chem. 39:125-189, 1988
Fersht, A.R.The hydrogen bond in molecular recognition. Trends Biochem. Sci. 12:301-304, 1987 |
|
|
|  | The Specific Interactions of a Macromolecule Depend on Weak, Noncovalent Bonds2
A macromolecular chain is held together by covalent bonds, which are strong enough to preserve the sequence of subunits for long periods of time. Although the sequence of subunits determines the information content of a macromolecule, utilizing that information depends largely on much weaker, noncovalent bonds. These weak bonds form between different parts of the same macromolecule and between different macromolecules. They therefore play a major part in determining both the three-dimensional structure of macromolecular chains and how these structures interact with one another.
The noncovalent bonds encountered in biological molecules are usually classified into three types: ionic bonds, hydrogen bonds, and van der Waals attractions. Another important weak force is created by the three-dimensional structure of water, which forces exposed hydrophobic groups together in order to minimize their disruptive effect on the hydrogen-bonded network of water molecules (see Panel 2-1, pp. 48-49). This expulsion from the aqueous solution generates what is sometimes thought of as a fourth kind of weak, noncovalent bond. These four types of weak attractive forces are the subject of Panel 3-1, pages 92-93.
In an aqueous environment each noncovalent bond is 30 to 300 times weaker than the typical covalent bonds that hold biological molecules together (Table 3-2) and only slightly stronger than the average energy of thermal collisions at 37°C (Figure 3-2). A single noncovalent bond - unlike a single covalent bond - is therefore too weak to withstand the thermal motions that tend to pull molecules apart. Large numbers of noncovalent bonds are needed to hold two molecular surfaces together, and these can form between two surfaces only when large numbers of atoms on the surfaces are precisely matched to each other (Figure 3-3). The exacting requirements for matching account for the specificity of biological recognition, such as occurs between an enzyme and its substrate.
As explained at the top of Panel 3-1, atoms behave almost as if they were hard spheres with a definite radius (their van der Waals radius). The requirement that no two atoms overlap limits the possible bond angles in a polypeptide chain (Figure 3-4). These and other steric interactions severely constrain the number of three-dimensional arrangements of atoms (or conformations) that are possible. Nevertheless, a long flexible chain such as a protein can still fold in an enormous number of ways. Each conformation will have a different set of weak intrachain interactions, and it is the total strength of these interactions that determines which conformations will form.
Most proteins in a cell fold stably in only one way: during the course of evolution the sequence of amino acid subunits in each protein has been selected so that one conformation is able to form many more favorable intrachain interactions than any other.
|
