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Computationally-guided optimization of small-molecule inhibitors of the Aurora A kinase-TPX2 protein-protein interaction
Free energy perturbation theory, in combination with enhanced sampling of protein-ligand binding modes, is evaluated in the context of fragment-based drug design, and used to design two new small-molecule inhibitors of the Aurora A kinase-TPX2 protein-protein interaction.
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| Published in: | Chemical communications (Cambridge, England) England), 2017-08, Vol.53 (67), p.9372-9375 |
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| Main Authors: | , , , , , , , , , , |
| Format: | Article |
| Language: | English |
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| cited_by | cdi_FETCH-LOGICAL-c378t-a69a7bb88307857e823a7eabad9ccfbe64629aa39a42f5f996c5ee504517e2493 |
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| cites | cdi_FETCH-LOGICAL-c378t-a69a7bb88307857e823a7eabad9ccfbe64629aa39a42f5f996c5ee504517e2493 |
| container_end_page | 9375 |
| container_issue | 67 |
| container_start_page | 9372 |
| container_title | Chemical communications (Cambridge, England) |
| container_volume | 53 |
| creator | Cole, Daniel J Janecek, Matej Stokes, Jamie E Rossmann, Maxim Faver, John C McKenzie, Grahame J Venkitaraman, Ashok R Hyvönen, Marko Spring, David R Huggins, David J Jorgensen, William L |
| description | Free energy perturbation theory, in combination with enhanced sampling of protein-ligand binding modes, is evaluated in the context of fragment-based drug design, and used to design two new small-molecule inhibitors of the Aurora A kinase-TPX2 protein-protein interaction. |
| doi_str_mv | 10.1039/c7cc05379g |
| format | article |
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| identifier | ISSN: 1359-7345 |
| ispartof | Chemical communications (Cambridge, England), 2017-08, Vol.53 (67), p.9372-9375 |
| issn | 1359-7345 1364-548X |
| language | eng |
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| source | Royal Society of Chemistry |
| subjects | Aurora Kinase A - antagonists & inhibitors Aurora Kinase A - chemistry Aurora Kinase A - metabolism Cell Cycle Proteins - antagonists & inhibitors Cell Cycle Proteins - chemistry Cell Cycle Proteins - metabolism Chemistry Humans Microtubule-Associated Proteins - antagonists & inhibitors Microtubule-Associated Proteins - chemistry Microtubule-Associated Proteins - metabolism Models, Molecular Molecular Dynamics Simulation Molecular Structure Nuclear Proteins - antagonists & inhibitors Nuclear Proteins - chemistry Nuclear Proteins - metabolism Protein Binding - drug effects Protein Kinase Inhibitors - chemistry Protein Kinase Inhibitors - pharmacology Small Molecule Libraries - chemistry Small Molecule Libraries - pharmacology |
| title | Computationally-guided optimization of small-molecule inhibitors of the Aurora A kinase-TPX2 protein-protein interaction |
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