Cargando…
Contributions of charge-density research to medicinal chemistry
This article reviews efforts in accurate experimental charge-density studies with relevance to medicinal chemistry. Initially, classical charge-density studies that measure electron density distribution via least-squares refinement of aspherical-atom population parameters are summarized. Next, inter...
Autores principales: | , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Union of Crystallography
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224464/ https://www.ncbi.nlm.nih.gov/pubmed/25485126 http://dx.doi.org/10.1107/S2052252514018867 |
_version_ | 1782343355135426560 |
---|---|
author | Dittrich, Birger Matta, Chérif F. |
author_facet | Dittrich, Birger Matta, Chérif F. |
author_sort | Dittrich, Birger |
collection | PubMed |
description | This article reviews efforts in accurate experimental charge-density studies with relevance to medicinal chemistry. Initially, classical charge-density studies that measure electron density distribution via least-squares refinement of aspherical-atom population parameters are summarized. Next, interaction density is discussed as an idealized situation resembling drug–receptor interactions. Scattering-factor databases play an increasing role in charge-density research, and they can be applied both to small-molecule and macromolecular structures in refinement and analysis; software development facilitates their use. Therefore combining both of these complementary branches of X-ray crystallography is recommended, and examples are given where such a combination already proved useful. On the side of the experiment, new pixel detectors are allowing rapid measurements, thereby enabling both high-throughput small-molecule studies and macromolecular structure determination to higher resolutions. Currently, the most ambitious studies compute intermolecular interaction energies of drug–receptor complexes, and it is recommended that future studies benefit from recent method developments. Selected new developments in theoretical charge-density studies are discussed with emphasis on its symbiotic relation to crystallography. |
format | Online Article Text |
id | pubmed-4224464 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | International Union of Crystallography |
record_format | MEDLINE/PubMed |
spelling | pubmed-42244642014-12-05 Contributions of charge-density research to medicinal chemistry Dittrich, Birger Matta, Chérif F. IUCrJ Feature Articles This article reviews efforts in accurate experimental charge-density studies with relevance to medicinal chemistry. Initially, classical charge-density studies that measure electron density distribution via least-squares refinement of aspherical-atom population parameters are summarized. Next, interaction density is discussed as an idealized situation resembling drug–receptor interactions. Scattering-factor databases play an increasing role in charge-density research, and they can be applied both to small-molecule and macromolecular structures in refinement and analysis; software development facilitates their use. Therefore combining both of these complementary branches of X-ray crystallography is recommended, and examples are given where such a combination already proved useful. On the side of the experiment, new pixel detectors are allowing rapid measurements, thereby enabling both high-throughput small-molecule studies and macromolecular structure determination to higher resolutions. Currently, the most ambitious studies compute intermolecular interaction energies of drug–receptor complexes, and it is recommended that future studies benefit from recent method developments. Selected new developments in theoretical charge-density studies are discussed with emphasis on its symbiotic relation to crystallography. International Union of Crystallography 2014-09-23 /pmc/articles/PMC4224464/ /pubmed/25485126 http://dx.doi.org/10.1107/S2052252514018867 Text en © Dittrich and Matta 2014 http://creativecommons.org/licenses/by/2.0/uk/ This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited. |
spellingShingle | Feature Articles Dittrich, Birger Matta, Chérif F. Contributions of charge-density research to medicinal chemistry |
title | Contributions of charge-density research to medicinal chemistry |
title_full | Contributions of charge-density research to medicinal chemistry |
title_fullStr | Contributions of charge-density research to medicinal chemistry |
title_full_unstemmed | Contributions of charge-density research to medicinal chemistry |
title_short | Contributions of charge-density research to medicinal chemistry |
title_sort | contributions of charge-density research to medicinal chemistry |
topic | Feature Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224464/ https://www.ncbi.nlm.nih.gov/pubmed/25485126 http://dx.doi.org/10.1107/S2052252514018867 |
work_keys_str_mv | AT dittrichbirger contributionsofchargedensityresearchtomedicinalchemistry AT mattacheriff contributionsofchargedensityresearchtomedicinalchemistry |