Comprehending renin inhibitor's binding affinity using structure-based approaches.
The performance of several structure-based design (SBD) approaches in predicting the binding affinity of diverse small molecule inhibitors co-crystallized to human renin was assessed to ascertain the modeling tool and method of choice required when dealing with structure-based lead optimization projects. Most of the SBD approaches investigated here were able to provide qualitative guidance, but quantitative accuracy as well as decisive discrimination between [in]actives is still not within reach. Such an outcome suggests that the current methods need improvement to capture the overall physics of the binding phenomenon for consistent applications in a lead optimization setting.
VMRD Global Discovery, Zoetis, 333 Portage Street, Kalamazoo, MI 49007, USA. Electronic address: govindan.subramanian@zoetis.com.
Govindan
G
Subramanian
Shashidhar N
SN
Rao
D001665:Binding Sites; D015195:Drug Design; D006801:Humans; D056004:Molecular Dynamics Simulation; D011480:Protease Inhibitors / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021281:Quantitative Structure-Activity Relationship; D012083:Renin / Q000378:metabolism; D000092502:Renin Inhibitors
D011480:Protease Inhibitors; D012083:Renin; D000092502:Renin Inhibitors
3D-QSAR; In silico modeling; MD simulation; MM-GB/SA; Renin inhibitor