Similarities and Differences between Crystal and Enzyme Environmental Effects on the Electron Density of Drug Molecules
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- 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
- Simon Grabowsky
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000607608500001&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1002/chem.202003978
- eISSN
- 1521-3765
- Externe Identifier
- Clarivate Analytics Document Solution ID: QH1DD
- PubMed Identifier: 33090581
- ISSN
- 0947-6539
- Ausgabe der Veröffentlichung
- 10
- Zeitschrift
- CHEMISTRY-A EUROPEAN JOURNAL
- Schlüsselwörter
- electron density
- electrostatic potential
- intermolecular interactions
- polarization
- protease inhibitor
- Paginierung
- 3407 - 3419
- Datum der Veröffentlichung
- 2021
- Status
- Published
- Titel
- Similarities and Differences between Crystal and Enzyme Environmental Effects on the Electron Density of Drug Molecules
- Sub types
- Article
- Ausgabe der Zeitschrift
- 27
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Abstract
- <jats:title>Abstract</jats:title><jats:p>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.</jats:p>
- Autoren
- 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
- Simon Grabowsky
- DOI
- 10.1002/chem.202003978
- eISSN
- 1521-3765
- ISSN
- 0947-6539
- Ausgabe der Veröffentlichung
- 10
- Zeitschrift
- Chemistry – A European Journal
- Sprache
- en
- Online publication date
- 2021
- Paginierung
- 3407 - 3419
- Datum der Veröffentlichung
- 2021
- Status
- Published
- Herausgeber
- Wiley
- Herausgeber URL
- http://dx.doi.org/10.1002/chem.202003978
- Datum der Datenerfassung
- 2023
- Titel
- Similarities and Differences between Crystal and Enzyme Environmental Effects on the Electron Density of Drug Molecules
- Ausgabe der Zeitschrift
- 27
Data source: Crossref
- 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.
- Addresses
- Department 2 - Biology/Chemistry, Institute of Inorganic Chemistry and Crystallography, University of Bremen, Leobener Str. 3 and 7, 28359 Bremen, Germany.
- Autoren
- 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
- Simon Grabowsky
- DOI
- 10.1002/chem.202003978
- eISSN
- 1521-3765
- Externe Identifier
- PubMed Identifier: 33090581
- PubMed Central ID: PMC7898524
- Funding acknowledgements
- SPring-8: 2013B1056
- Studienstiftung des Deutschen Volkes:
- Australian Research Council: DP110105347
- Deutsche Forschungsgemeinschaft: GR 4451/1-1
- Open access
- true
- ISSN
- 0947-6539
- Ausgabe der Veröffentlichung
- 10
- Zeitschrift
- Chemistry (Weinheim an der Bergstrasse, Germany)
- Schlüsselwörter
- Pharmaceutical Preparations
- Ligands
- Electrons
- Static Electricity
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2021
- Open access status
- Open Access
- Paginierung
- 3407 - 3419
- Datum der Veröffentlichung
- 2021
- Status
- Published
- Publisher licence
- CC BY-NC
- Datum der Datenerfassung
- 2020
- Titel
- Similarities and Differences between Crystal and Enzyme Environmental Effects on the Electron Density of Drug Molecules.
- Sub types
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 27
Files
https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/chem.202003978 https://europepmc.org/articles/PMC7898524?pdf=render
Data source: Europe PubMed Central
- 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.
- Autoren
- 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
- Simon Grabowsky
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/33090581
- DOI
- 10.1002/chem.202003978
- eISSN
- 1521-3765
- Externe Identifier
- PubMed Central ID: PMC7898524
- Funding acknowledgements
- Deutsche Forschungsgemeinschaft: GR 4451/1-1
- Australian Research Council: DP110105347
- Studienstiftung des Deutschen Volkes:
- SPring-8: 2013B1056
- Ausgabe der Veröffentlichung
- 10
- Zeitschrift
- Chemistry
- Schlüsselwörter
- electron density
- electrostatic potential
- intermolecular interactions
- polarization
- protease inhibitor
- Electrons
- Ligands
- Pharmaceutical Preparations
- Static Electricity
- Sprache
- eng
- Country
- Germany
- Paginierung
- 3407 - 3419
- Datum der Veröffentlichung
- 2021
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2021
- Titel
- Similarities and Differences between Crystal and Enzyme Environmental Effects on the Electron Density of Drug Molecules.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 27
Data source: PubMed
- Beziehungen:
- Property of