Structure-based virtual screening strategy applied to the search for new modulating agents of the hNv1 proton channel

CHAULET MARIA VIRGINIA; GANTNER MELISA; LLANOS MANUEL; MILESI VERONICA; GAVERNET LUCIANA

Conferencia; Reunion conjunta de sociedades de biociencias; 2023

hHv1 channel plays a fundamental role in various physiological processes such as innate and adaptive immunity, insulin secretion, and sperm capacitation. Its monomer is composed of 273 amino acids, however, it may also works as a dimer. This channel mediates a highly selective passage of H+ without present a pore domain.We have recently demonstrated that ATP exerts an activating effect on hHv1, mainly mediated through the interaction of the ATP phosphate groups with positive residues in the intracellular side of the channel.In this investigation the virtual screening identified 93 candidates that interacts with better score than the reference ligands. They showed an interaction pattern similar to ATP/ADP into the active site. The following step is to acquire and test the effects of the candidates on hHv1 by Patch Clamp protocols to evaluate the performance of the computational models.