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.

Saved in:
Bibliographic Details
Published in:Chemical communications (Cambridge, England) England), 2017-08, Vol.53 (67), p.9372-9375
Main Authors: 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
Format: Article
Language:English
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
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
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1359-7345
1364-548X
DOI:10.1039/c7cc05379g