Atomistic-Level Structural Insight into Vespa Venom (Ves a 1) and Lipid Membrane Through the View of Molecular Dynamics Simulation.

This study used all-atom molecular dynamics simulations to investigate the structural dynamics of Ves a 1, a phospholipase from venom, and its interactions within a lipid membrane environment, both alone and in the presence of the inhibitor voxilaprevir. Simulations conducted over 1 µs for triplicate runs demonstrated system stability and convergence of structural properties. Our findings reveal that Ves a 1 engages in dynamic interactions with the lipid bilayer, involving key regions such as its lids, catalytic triad, and auxiliary site. The presence of voxilaprevir was observed to subtly alter these membrane interaction patterns and influence the enzyme's catalytic area, reflecting the inhibitor's impact within its physiological context. These results emphasize the crucial role of the lipid bilayer in shaping enzyme function and highlight voxilaprevir as a promising candidate for further inhibitor development, offering vital insights for rational drug design targeting membrane-associated proteins.