Protein flexibility in docking and virtual screening on the beta 2 adrenergic receptor

ZAMBRANA, ROMINA; CAVASOTTO, CLAUDIO N

Buenos Aires

Congreso; Drug Discovery for Neglected Diseases International Congress 2018; 2018

Recently, insecticides that disrupt G protein-coupled receptor (GPCR) targets in the arthropod vectors (that transmited infectious diseases, such as dengue, yellow fever, Zika and leishmaniasis) have been proposed against resistant pest populations. In the past, in silico methods have been successful to identify drug leads using docking-based virtual screening. However, these methods generally do not consider the flexibility of the protein, decreasing the effectiveness of finding new drugs. In this work, we focused on the β2 Adrenergic Receptor (β2AR), which is involved in the treatment of multiple human diseases. The aims of this study are to analyze how the lack of flexibility for the agonist and antagonist/inverse-agonist modes of β2AR structures impacts on molecular docking. On the other hand, we study the impact of flexibility on enrichment in virtual screening for the same receptor using the rigid receptor docking approach and the Receptor Ensemble Docking method.