Similarities and differences between crystal and enzyme environmental effects on the electron density of drug molecules

Florian Kleemiss, Erna K. Wieduwilt, Emanuel Hupf, Ming W. Shi, Scott G. Stewart, Dylan Jayatilaka, Michael J. Turner, Kunihisa Sugimoto, Eiji Nishibori, Tanja Schirmeister, Thomas C. Schmidt, Bernd Engels (+1 others)
The crystal interaction density is generally assumed to be a suitable measure of the polarization of a low‐molecular weight ligand inside an enzyme, but this approximation has seldomly been tested and has never been quantified before. In this study, we compare the crystal interaction density and the interaction electrostatic potential for a model compound of loxistatin acid (E64c) with those inside cathepsin B, in solution and in vacuum. We apply QM/MM calculations and experimental quantum
more » ... mental quantum crystallography to show that the crystal interaction density is indeed very similar to the enzyme interaction density. Less than 0.1e are shifted between these two environments in total. However, this has non‐negligible consequences for derived properties.
doi:10.48350/150766 fatcat:74pf6dzaqfgjzlmkvkjd6qmxne