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RESEARCH PRODUCT
Similarities and differences between crystal and enzyme environmental effects on the electron density of drug molecules
Michael J. TurnerThomas C. SchmidtSimon GrabowskySimon GrabowskyEiji NishiboriTanja SchirmeisterErna K. WieduwiltErna K. WieduwiltBernd EngelsEmanuel HupfScott G. StewartFlorian KleemissFlorian KleemissKunihisa SugimotoMing W. ShiDylan Jayatilakasubject
Electron densityStatic ElectricityElectrons010402 general chemistryLigands01 natural sciencesCatalysisprotease inhibitor540 ChemistryMoleculeelectron densityPolarization (electrochemistry)Quantumchemistry.chemical_classificationpolarizationFull Paperintermolecular interactions010405 organic chemistryOrganic ChemistryIntermolecular forceEnzyme InteractionGeneral ChemistryFull Papers0104 chemical sciences3. Good healthMolecular RecognitionEnzymeelectrostatic potentialchemistryPharmaceutical PreparationsLoxistatinChemical physics570 Life sciences; biologydescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-01-14 |