NMR Data-Driven Docking of HDM2-Inhibitor Complexes

Autor:	Xavier Fradera, Michael H. Reutershan, Michelle R. Machacek, B. Wesley Trotter, Mark A. McCoy
Rok vydání:	2021
Předmět:	Models Molecular Binding Sites Magnetic Resonance Spectroscopy Protein Conformation Organic Chemistry Molecular Medicine Proteins Ligands Molecular Biology Biochemistry Protein Binding
Zdroj:	Chembiochem : a European journal of chemical biology. 23(6)
ISSN:	1439-7633
Popis:	We present an automated NMR-guided docking workflow that can be used to generate models of protein-ligand complexes based on data from NOE NMR experiments. The first step is to generate a number of intermolecular distance constraints from experimental NOE data. Then, the ligand is docked on an ensemble of receptor structures to account for protein flexibility, and multiple poses are generated. Finally, we use the NOE-based constraints to filter and score docking poses based on the percentage of NOE constraints that are consistent with protein-ligand interatomic distances. This workflow was successfully used during a lead optimization project to generate models of synthetic protein-protein interaction (PPI) inhibitors bound to the HDM2 protein.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0be041247caf23dd8a9121996305af82 https://pubmed.ncbi.nlm.nih.gov/35104390 Zobrazit plný text záznamu Plný text