6W4G

Hepatitis C virus polymerase NS5B with RO inhibitor for SAR studies

Summary for 6W4G

• Entry DOI: 10.2210/pdb6w4g/pdb
• Descriptor: NS5B, 5-[[(2~{S})-4-[1,1-bis(oxidanylidene)-1,2-benzothiazol-3-yl]-2-~{tert}-butyl-3-oxidanyl-5-oxidanylidene-2~{H}-pyrrol-1-yl]methyl]-2-fluoranyl-benzenecarbonitrile (3 entities in total)
• Functional Keywords: hcv pol, ns5b, polymerase, transferase-transferase inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Hepatitis C virus genotype 1b (isolate BK) (HCV)
• Total number of polymer chains: 2
• Total formula weight: 127406.08

Authors

Harris, S.F. (deposition date: 2020-03-10, release date: 2020-11-04, Last modification date: 2024-10-23)

Primary citation

Tosstorff, A.,Cole, J.C.,Taylor, R.,Harris, S.F.,Kuhn, B.
Identification of Noncompetitive Protein-Ligand Interactions for Structural Optimization.
J.Chem.Inf.Model., 60:6595-6611, 2020

PubMed Abstract: For efficient structure-guided drug design, it is important to have an excellent understanding of the quality of interactions between the target receptor and bound ligands. Identification and characterization of poor intermolecular contacts offers the possibility to focus design efforts directly on ligand regions with suboptimal molecular recognition. To enable a more straightforward identification of these in a structural model, we use a suitably enhanced version of our previously introduced statistical ratio of frequencies () approach. This allows us to highlight protein-ligand interactions and geometries that occur much less often in the Protein Data Bank than would be expected from the exposed surface areas of the interacting atoms. We provide a comprehensive overview of such noncompetitive interactions and geometries for a set of common ligand substituents. Through retrospective case studies on congeneric series and single-point mutations for several pharmaceutical targets, we illustrate how knowledge of noncompetitive interactions could be exploited in the drug design process.

PubMed: 33085891
DOI: 10.1021/acs.jcim.0c00858

Experimental method

X-RAY DIFFRACTION (1.95 Å)