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...
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| Format: | Article |
| Language: | English |
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International Union of Crystallography
2014-11-01
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| Series: | IUCrJ |
| Subjects: | |
| Online Access: | http://scripts.iucr.org/cgi-bin/paper?S2052252514018867 |
| _version_ | 1819002343368163328 |
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| author | Birger Dittrich Chérif F. Matta |
| author_facet | Birger Dittrich Chérif F. Matta |
| author_sort | Birger Dittrich |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T23:03:36Z |
| format | Article |
| id | doaj.art-ac4550ea716b4d1892254623932a9cf1 |
| institution | Directory Open Access Journal |
| issn | 2052-2525 |
| language | English |
| last_indexed | 2024-12-20T23:03:36Z |
| publishDate | 2014-11-01 |
| publisher | International Union of Crystallography |
| record_format | Article |
| series | IUCrJ |
| spelling | doaj.art-ac4550ea716b4d1892254623932a9cf12022-12-21T19:23:55ZengInternational Union of CrystallographyIUCrJ2052-25252014-11-011645746910.1107/S2052252514018867lc5061Contributions of charge-density research to medicinal chemistryBirger Dittrich0Chérif F. Matta1Institut für Anorganische und Angewandte Chemie, Martin-Luther-King-Platz 6, 20146 Hamburg, GermanyDepartment of Chemistry and Physics, Mount Saint Vincent University, Halifax, Nova Scotia B3M 2J6, CanadaThis 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.http://scripts.iucr.org/cgi-bin/paper?S2052252514018867charge-density researchmedicinal chemistrydrug designinvariomHansen–Coppens multipole modelquantum theory of atoms in molecules |
| spellingShingle | Birger Dittrich Chérif F. Matta Contributions of charge-density research to medicinal chemistry IUCrJ charge-density research medicinal chemistry drug design invariom Hansen–Coppens multipole model quantum theory of atoms in molecules |
| 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 | charge-density research medicinal chemistry drug design invariom Hansen–Coppens multipole model quantum theory of atoms in molecules |
| url | http://scripts.iucr.org/cgi-bin/paper?S2052252514018867 |
| work_keys_str_mv | AT birgerdittrich contributionsofchargedensityresearchtomedicinalchemistry AT cheriffmatta contributionsofchargedensityresearchtomedicinalchemistry |