Theoretical estimation of the dielectric properties of an enzyme active site

A theoretical investigation of the solvatochromism of 4-carbamidopyridinium cyclopentadienylide (CPCP) has been carried out to understand the environmental effect of the enzyme active site. The λ_max values for CPCP in various solvents and in the binding pocket of horse liver alcohol dehydrogenase (LADH) have been calculated using the INDO/S method. Since the shape of CPCP is not spherical, the cavity radius was considered as an adjustable parameter that controls the strength of the reaction field in the INDO/S calculation. To investigate the medium effect of the enzyme binding pocket correctly, the specific interaction, such as a ligation of Zn²⁺, should be considered in the calculation of the λ_max values. By comparing the experimental λ_max value for CPCP in LADH with the calculated values for the Zn²⁺-(SH)₂-Im-CPCP complex, we have found that the medium effect of the LADH binding pocket is similar to that of organic solvents such as octan-1-ol(ε = 10.3) and CH₂Cl₂(ε = 8.9).