Identifying Structural Features Related to the Biological Activity of a Series of AT1 Antagonists from Fragment-based Drug Design

Title:Identifying Structural Features Related to the Biological Activity of a Series of AT1 Antagonists from Fragment-based Drug Design

Volume: 21 Issue: 6

Author(s): Danielle da C. Silva, Vinícius G. Maltarollo and Kathia M. Honorio

Affiliation:

Keywords: Angiotensin II, drug design, fragment-based method, hypertension, molecular modeling.

Abstract: Antagonists of AT₁ receptor are interesting substances to develop drugs that can be used for the treatment of hypertension and other diseases that affect the cardiovascular system. This study investigates the main interactions between various AT₁ antagonists and the biological target by applying fragment-based drug design (Hologram QSAR - HQSAR). The proposed HQSAR model yielded significant correlation coefficients (q² = 0.764 and r² = 0.914), indicating that the method is rigorous and reliable. All models were externally validated using a test set and the results showed good agreement between the experimental and predicted data (r² _test = 0.740). Therefore, our model can positively contribute to understand the structural features involved in the main interactions between the AT¹ antagonists and the residues of the binding site.

Cite this article as:

Silva da C. Danielle, Maltarollo G. Vinícius and Honorio M. Kathia, Identifying Structural Features Related to the Biological Activity of a Series of AT1 Antagonists from Fragment-based Drug Design, Protein & Peptide Letters 2014; 21 (6) . https://dx.doi.org/10.2174/092986652106140425122007