Protein conformational flexibility modulates kinetics and thermodynamics of drug binding
An understanding of the dynamics of drug binding and unbinding processes is important for drug discovery. Here, the authors give insights into the binding mechanism of small drug-like molecules to human Hsp90 by combining thermodynamics and kinetics studies as well as molecular dynamics simulations.
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2017-12-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-017-02258-w |
| _version_ | 1818342103902584832 |
|---|---|
| author | M. Amaral D. B. Kokh J. Bomke A. Wegener H. P. Buchstaller H. M. Eggenweiler P. Matias C. Sirrenberg R. C. Wade M. Frech |
| author_facet | M. Amaral D. B. Kokh J. Bomke A. Wegener H. P. Buchstaller H. M. Eggenweiler P. Matias C. Sirrenberg R. C. Wade M. Frech |
| author_sort | M. Amaral |
| collection | DOAJ |
| description | An understanding of the dynamics of drug binding and unbinding processes is important for drug discovery. Here, the authors give insights into the binding mechanism of small drug-like molecules to human Hsp90 by combining thermodynamics and kinetics studies as well as molecular dynamics simulations. |
| first_indexed | 2024-12-13T16:09:22Z |
| format | Article |
| id | doaj.art-8cad50c6a80c4f728aa29dd8ed5e414e |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-12-13T16:09:22Z |
| publishDate | 2017-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-8cad50c6a80c4f728aa29dd8ed5e414e2022-12-21T23:38:59ZengNature PortfolioNature Communications2041-17232017-12-018111410.1038/s41467-017-02258-wProtein conformational flexibility modulates kinetics and thermodynamics of drug bindingM. Amaral0D. B. Kokh1J. Bomke2A. Wegener3H. P. Buchstaller4H. M. Eggenweiler5P. Matias6C. Sirrenberg7R. C. Wade8M. Frech9iBET - Instituto de Biologia Experimental e TecnológicaMolecular and Cellular Modeling Group, Heidelberg Institute for Theoretical StudiesMolecular Pharmacology, Merck KGaAMolecular Interactions and Biophysics, Merck KGaAMedicinal Chemistry, Merck KGaAMedicinal Chemistry, Merck KGaAiBET - Instituto de Biologia Experimental e TecnológicaCellular Pharmacology - OncologyMolecular and Cellular Modeling Group, Heidelberg Institute for Theoretical StudiesMolecular Interactions and Biophysics, Merck KGaAAn understanding of the dynamics of drug binding and unbinding processes is important for drug discovery. Here, the authors give insights into the binding mechanism of small drug-like molecules to human Hsp90 by combining thermodynamics and kinetics studies as well as molecular dynamics simulations.https://doi.org/10.1038/s41467-017-02258-w |
| spellingShingle | M. Amaral D. B. Kokh J. Bomke A. Wegener H. P. Buchstaller H. M. Eggenweiler P. Matias C. Sirrenberg R. C. Wade M. Frech Protein conformational flexibility modulates kinetics and thermodynamics of drug binding Nature Communications |
| title | Protein conformational flexibility modulates kinetics and thermodynamics of drug binding |
| title_full | Protein conformational flexibility modulates kinetics and thermodynamics of drug binding |
| title_fullStr | Protein conformational flexibility modulates kinetics and thermodynamics of drug binding |
| title_full_unstemmed | Protein conformational flexibility modulates kinetics and thermodynamics of drug binding |
| title_short | Protein conformational flexibility modulates kinetics and thermodynamics of drug binding |
| title_sort | protein conformational flexibility modulates kinetics and thermodynamics of drug binding |
| url | https://doi.org/10.1038/s41467-017-02258-w |
| work_keys_str_mv | AT mamaral proteinconformationalflexibilitymodulateskineticsandthermodynamicsofdrugbinding AT dbkokh proteinconformationalflexibilitymodulateskineticsandthermodynamicsofdrugbinding AT jbomke proteinconformationalflexibilitymodulateskineticsandthermodynamicsofdrugbinding AT awegener proteinconformationalflexibilitymodulateskineticsandthermodynamicsofdrugbinding AT hpbuchstaller proteinconformationalflexibilitymodulateskineticsandthermodynamicsofdrugbinding AT hmeggenweiler proteinconformationalflexibilitymodulateskineticsandthermodynamicsofdrugbinding AT pmatias proteinconformationalflexibilitymodulateskineticsandthermodynamicsofdrugbinding AT csirrenberg proteinconformationalflexibilitymodulateskineticsandthermodynamicsofdrugbinding AT rcwade proteinconformationalflexibilitymodulateskineticsandthermodynamicsofdrugbinding AT mfrech proteinconformationalflexibilitymodulateskineticsandthermodynamicsofdrugbinding |