| Institution: | 1. Department 2 – Biology/Chemistry, Institute of Inorganic Chemistry and Crystallography, University of Bremen, Leobener Str. 3 and 7, 28359 Bremen, Germany;2. School of Molecular Sciences, University of Western Australia, 35 Stirling Highway, Perth WA 6009, Australia;3. Japan Synchrotron Radiation Research Institute, SPring-8, 1-1-1 Kouto, Sayo-cho, Sayo-gun, Hyogo 679-5198, Japan;4. Division of Physics, Faculty of Pure and Applied Sciences, Tsukuba Research Center for Energy Materials Science, University of Tsukuba, Tsukuba, Japan;5. Institute of Pharmaceutical and Biomedical Sciences, Johannes-Gutenberg University Mainz, Staudingerweg 5, 55128 Mainz, Germany;6. Institute for Physical and Theoretical Chemistry, Julius-Maximilians-University Würzburg, Emil-Fischer-Str. 42, 97074 Würzburg, Germany |
| Abstract: | 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 crystallography to show that the crystal interaction density is indeed very similar to the enzyme interaction density. Less than 0.1 e are shifted between these two environments in total. However, this difference has non-negligible consequences for derived properties. |
