300 6. INTERACTIONS OF INHIBITORS WITH ENZYMES 



INTERACTIONS OF HYDROCARBON CHAINS 



The interactions of hydrocarbon groups on the substrate or inhibitor 

 with hydrocarbon or nonpolar residues on the enzyme may occasionally 

 contribute a significant fraction of the total binding energy. Dispersion 

 forces only need be considered here. Calculation of the dispersion energies 

 between (— CHg— )„ chains in paraffin crystals was reported by Miiller 

 (1936) and satisfactory agreement with the heats of sublimation was ob- 

 tained. However, the orientation of the chains in these crystals is unlikely 

 to be that found in enzyme interactions and thus it will be of interest to 

 present some tentative calculations based on reasonable models. It is 

 relatively easy to determine the dispersion energy of two adjacent hydro- 

 carbon chains in any assumed configuration, but the energy terms for water 

 displacement present some difficulties since the changes in water structure 

 during the interaction are not clearly undestood. 



Neglecting the water temporarily, a simple calculation of the dispersion 

 energy assuming two parallel (— CH2— ),, chains separated by their van der 

 Waals' radii (4.2 A between chain axes) gives — 0.17 kcal/mole for each 

 -CH2— unit (Z = 6, Ro = 4.50 ml/mole in Eq. 6-69). If the two chains 

 are assumed to be oriented for closest fit, with each — CH2— midway be- 

 tween those on the other chain (see Fig. 6-7), and the interactions of each 

 — CHg— with all others on the adjacent chain are considered, the disper- 

 sion energy may be as high as — 0.76 kcal/mole, but it is likely that such 

 perfect orientation would be achieved only under very special conditions. 

 The change in dispersion energy involved in the displacement of water 

 molecules may be calculated to be — 0.19 kcal/mole for each — CHg — 

 unit, assuming that an average of two water molecules are in contact with 

 each unit before reaction. Thus the total interaction energy for a single 

 — CH2— unit would be around 0.36-0.95 kcal/mole, depending on the 

 degree of fit, taking into account the dispersion energy only. If the for- 

 mation of hydrogen bonds between water molecules occurs as the result 

 of the displacement, the over-all interaction energy might be greater than 

 these figures. The binding energies for some aliphatic sulfates with serum 

 albumin are: octyl sulfate, — 5.01 kcal/mole; decyl sulfate, — 6.03 kcal/ 

 mole, and dodecyl sulfate, — 7.22 kcal/mole (Klotz, 1949). The interaction 

 energy per — CHg— unit would thus be about 0.55 kcal/mole, which is 

 within the calculated range. In any event it is evident that such hydro- 

 carbon chains, if oriented properly for interaction with nonpolar regions 

 of the enzyme, can contribute appreciably to the binding energy. Partic- 

 ularly high energy values might result from the position of a hydrocarbon 

 chain within a slit on the protein or if the mobility of the protein side-chains 

 allowed partial or complete enclosure of the chain. 



