Development of accurate binding affinity predictions of novel renin inhibitors through molecular docking studies

In this study, an attempt was made to explore a possible correlation between different docking scoring functions (Glide InducedFit docking score and GOLD's GoldScore and ChemScore) and binding energy values of a set of renin inhibitors, using linear regression model. The renin inhibitors under study are characterized by known bound to the receptor crystal structures possessing a great variety of pharmacophore groups and a wide range of IC50 values. Linear regression models were derived to relate the docking scoring function and pIC50 values of renin inhibitors under study. The developed derived models are seeking to be helpful for the rational design of new, more potent renin inhibitors.

Graphical abstractBinding mode of aliskiren as produced from crystallographic data. The protein backbone is shown in ribbons. Residues of the binding site are displayed as grey sticks and aliskiren as ball and sticks. The right panel shows a zoom in the active site and the formed H-bonds with aliskiren.Figure optionsDownload full-size imageDownload high-quality image (138 K)Download as PowerPoint slideResearch highlights▶ The GOLD docking program seems to be superior among others in the study of renin inhibitors. ▶ Among the scoring function of GOLD, GoldScore demonstrates superior scoring reliability. ▶ There is a significant correlation between GoldScore and pIC50 values of renin inhibitors. ▶ Active renin inhibitors presuppose interactions with the aspartate residues of renin (Asp 32 or Asp 215) and the S3sp sub pocket.