INTERMOLECULAR FORCES AND INTERACTION ENERGY 205 



of simple molecules in a vacuum is one of degree only: the former are gener- 

 ally more complex because of the multiple groups involved, the different 

 types of forces simultaneously operative, and the presence of the solvent 

 water. The various forces involved will be discussed briefly, following which 

 certain applications to situations of importance in protein interactions will 

 be made. These possible forces between enzymes and inhibitors may be 

 classified in the following manner, although it should be emphasized that 

 at the ultimate level all forces are electrostatic in nature. 



I. Covalent: bond formed by the sharing of an electron pair between two atoms 



II. Electrostatic: interaction between atoms or groups that possess permanent electric 

 charges 



A. Ion- ion interaction 



B. lon-dipole interaction 



C. Dipole-dipole interaction 



D. Hydrogen bonds 



III. Induced: interaction resulting from the induction of a dipole in a group subjected 



to the electric field of a permanently charged group 



A. Ion-induced dipole interaction 



B. Dipole-induced dipole interaction 



IV. Electrokinetic: interaction between neutral nonpolar groups due to mutual in- 



duction of fluctuating dipoles — also called dispersion or London 

 forces 



V. Short-range repulsive: due to the electrostatic repulsion between electrons in 



the overlapping of the electron clouds of two atoms 



These forces differ from one another principally in their directional char- 

 acter and the influence of orientation, their variation with the distance 

 between the interacting groups, and the amount of energy they involve at 

 the usual interaction distances. In some cases of inhibition, one type of 

 force dominates, but in others the binding is due to the simultaneous opera- 

 tion of several forces, each of which contibutes to the total interaction 

 energy. 



The Covalent Bond 



A normal covalent bond exists between atoms when two electrons of 

 opposite spin moment are shared between them. The bond energy may be 

 attributed to the resonance of the electrons between the atoms. The elec- 

 tron density in a covalent bond is thus greatest in the region between the 

 atoms. Such bonds have three important characteristics: (a) they are direct- 

 ed so that when two or more bonds are associated with an atom they 

 tend to assume a fixed angle to one another, (6) they, of all types of inter- 



