Ensemble docking to difficult targets in early-stage drug discovery: Methodology and application to fibroblast growth factor 23.

ABSTRACT: Ensemble docking is now commonly used in early-stage in silico drug discovery and can be used to attack difficult problems such as finding lead compounds which can disrupt protein-protein interactions. We give an example of this methodology here, as applied to fibroblast growth factor 23 (FGF23), a protein hormone that is responsible for regulating phosphate homeostasis. The first small-molecule antagonists of FGF23 were recently discovered by combining ensemble docking with extensive experimental target validation data (Science Signaling, 9, 2016, ra113). Here, we provide a detailed account of how ensemble-based high-throughput virtual screening was used to identify the antagonist compounds discovered in reference (Science Signaling, 9, 2016, ra113). Moreover, we perform further calculati

SUBMITTER: Velazquez HA 

PROVIDER: S-EPMC7983124 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature