Exhaustive computational analysis of Ascaris suum?s NPA- ligand interaction. Searching for a gate in

FERNANDO ZAMARREÑO; JUAN FRANCISCO VISO; MARÍA JULIA AMUNDARAIN; MARCELO D. COSTABEL

La Plata

Congreso; XLVII Reunión Anual de la Sociedad Argntina de Biofísica; 2018

Sociedad Argentina de Biofísica

ematode polyprotein allergens (NPAs) are atypical lipid-binding proteins. Due tothe fact that these proteins have no counterparts in vertebrates and becausehelminthes parasites have a restricted lipid metabolism, and must acquire simpleand complex lipids from their hosts, NPAs represent potential targets for drugdesign.ABA-1A is the most common repeating unit of the NPA of Ascaris suum. In thiswork we aim at understanding the molecular basis of ABA-1-A - lipid interaction toevaluate them as potential anthelmintics drug targets.Using an in-house developed software and APBS, the solutions of the Poisson?Boltzmann equation were used to calculate the electrostatic interaction energybetween ABA-1-A and oleate for 3000 possible configurations. In order to selectthe most suitable ABA-1-A - oleate configurations, the difference between theelectrostatic energy of a system compound by ABA-1-A and oleate, and theelectrostatic energy calculated for both, ABA-1-A and oleate, individually werecalculated for all relative positions. Lowest values were considered as bestinteractions.A small group of minimum electrostatic energy for ABA-1-A - oleate relativeposition was selected, in order to use them as initial configurations for MolecularDynamics (MD) study of ABA-1-A - oleate interaction.Results from MD suggest that ABA1-A seems to have more than one putative gatefor oleate entrance to the protein hydrophobic core, like other Lipid BindingPorteins, such as Rat LFABP. Additionally, we were able to identificate residues withhigh interaction with oleate.