Earl Frieden Florida State University Tallahassee, 32306
Nan-Covalent Interactions Key to biological flexibility and specificity
The non-covalent interactions of biological molecules provide the flexihility and specificity required in most important hiological processes relating to the regulation of metabolism. They provide a sharp contrast with covalent biochemical compounds which supply the structural firmness and the energy reservoir for living systems. Why do antibodies react so specifically and so strongly with their respective antigens? What is the basis for deoxyribonucleic acid (DNA) being found most frequently in pairs, tightly associated in a double stranded helix. Why do hormones attach reversibly to target cell memhranes and not to the membranes of other cells? How is iron transported and fed principally to those cells which need it for hemoglobin hiosynthesis? Why does the hemoglobin molecule consist of an aggregate of four polypeptide chains? How can the substitution of one out of 300 amino acids in the hemoglobin mutation of sickle cell anemia distort the shape of the molecule so that the entire cell is forced to assume an abnormal form? The concept which unifies the explanation for these and a host of other important biological phenomena may he described as intermolecular interactions of the non-covalent type or simply "non-covalent interactions." This distinguishes these interactions from the more common comhination of atoms andlor molecules by covalent hond formation. The typical molecule is an assembly of atoms which is held together very tightly by one or more covalent honds. Covalent honds identify the typical highly stable intramolecular linkage formed by two atoms which share electrons. Biological systems are dependent on covalent compounds as sources of energy for the myriad of energy requiring processes and for most of the structural elements of all organisms a t many different levels. But for the conduct of their business, for the regulation of the rates and direction of biological reactions, living systems need more flexihility. This flexihility is provided by the utilization of a large number of non-covalent interactions to bring two or more molecules together to realize a specific biological objective. The formation of a non-covalent complex hetween molecules A and B rather than a covalent bonded compound, A-B, provides a rapid and reversible way to associate two molecules with properties and functions of which neither molecule alone is capable. I t permits the reutilization of vital molecules such as enzymes, hormones, and vitamins, which may he difficult to synthesize or to obtain from the environment. At the same time, non-covalent interactions do not sacrifice the options for specificity which are so necessary for unique biochemical reactions. Thus adaptability, selectivity, reversihility and economy are promoted by these subtle chemical linkages between molecules of all sizes found in living systems. Complementary Structures
As might he expected, these intermolecular non-covalent interactions form rather weak honds compared to covalent linkages. A single covalent bond has a heat of formation in the range of 50-150 kcallmole. A typical non-covalent "hond", e.g., the hydrogen hond, requires only 2-10 kcall mole as shown in the table ( I ) . The firmness of non-covalent interactions arises from their multiplicity and, some754 / Journal of ChemicalEducation
NonCovalent Bonds and Interactions in Proteins" Approximate Stabilization Energy k c 4 mole-'
/
Hydrogen bond between peptiaer
\ /
Hydrogen bond between neutral groups
/ N
I I
'H-O/C\
Hydrogen bond between neutral and charged groups Hydrogen bond between peptide and R group Hydrogen bond or ionic bond between charged groups strongly dependent on distance
>C=O---H+
-NH,
a
-\ e!c-/
CH, CH,
I
Hydrophobic interaction
I
96 H3C\
/CHa CH
H&\
HYdlDPhobiC interaction of aromatic -tacking rings
/CH, CH
I
I
Hydrophobic interaction
1.5
Hydrophobic interaction between R w o u o lor Dart
0.3 per CH,
'I
ZFrom reference
"ting the caiboxyi group to the bond
(I).
times, cooperativity. The summation of forces from many non-covalent interactions can confer remarkable stability to two interacting macromolecules such as two DNA strands or an antigen-antihody precipitate. The prospects for multiple interactions. particularlv for macromolecules. enhanced if two molecuies assume a comple: are mentary rather than identical spatial relationships. In 1940 Linus Pauling and Max Delbruck ( 2 ) pointed out that the processes of synthesis and folding of highly complex molecules in the living cell involve, in addition to covalent bond formation, an appreciable number of intermolecular interactions. These interactions confer stahility to systems of two molecules with complementary structures in Drover juxtaposition, rather tha
