Identifying Structural Features Related to the Biological Activity of a Series of AT1 Antagonists from Fragment-based Drug Design
Danielle da C. Silva, Vinícius G. Maltarollo and Kathia M. Honorio
Affiliation: School of Arts, Sciences, and Humanities, University of Sao Paulo, Sao Paulo, Brazil.
Keywords: Angiotensin II, drug design, fragment-based method, hypertension, molecular modeling.
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
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