Pemodelan Homologi Komparatif FABP Belalang Kembara (Locusta migratoria) Dengan PHYRE2 dan Skrining Virtual Inhibitor Potensial

Comparative Homology Modeling of Fatty-Acid Binding Protein (FABP) from Locusta migratoria Using Phyre2 and Virtual Screening for Potent Inhibitors

Abstract

The outbreak of locusta migratoria has caused a local crisis in production and cultivation of agricultural crops in East Nusa Tenggara Province. FABP (Fatty Acid-Binding Protein) plays an important role in transporting fatty acids from cytoplasm into mitochondria to generate ATP energy for locusta to fly and migrate. FABP inhibition is an attractive strategy to be exploited for novel insecticide development. Comparative homology modeling using Phyre2 had been used to generate two FABP models built from desert locusta (Schistocerca gregaria, 98% percent identity) and mice (Mus musculus, 40% percent identity) FABP protein as templates. Both FABP models showed an acceptable quality of stereochemistry and structural energy with lower atomic clash scores after refinement. Virtual screening identified potent inhibitor candidates with highest affinity energies which are (i) a heterocyclic compound C00628966 (-10.2 kcal/mol) and (iii) an imidazole derivative C15721579 (-8.5 kcal/mol) that were stabilized through a hydrogen bond with Ser53 also (iii) a pyrimidine derivative C73698912 (-8.1 kcal/mol) stabilized through hydrogen bonds with Thr57, Thr62 and Ser55. Their interactions resemble inhibitors that have been known to inhibit homologous FABP in humans. Therefore, these compounds warrant further in vitro validation and assay for development of selective insecticides to control locusta population.