High-affinity selective inhibitor against phospholipase A(2) (PLA(2)): a computational study

作者：Chinnasamy Sathishkumar; Chinnasamy Selvakkumar; Muthusamy Karthikeyan^*

来源：Journal of Receptors and Signal Transduction, 2016, 36(2): 111-118.

DOI：10.3109/10799893.2015.1056306

• IFD
• MD simulation
• molecular modeling
• PLA(2)
• QPLD

Phospholipase A(2) (PLA(2)) is the most abundant protein found in snake venom. PLA(2) induces a variety of pharmacological effects such as neurotoxicity, myotoxicity and cardiotoxicity as well as anticoagulant, hemolytic, anti-platelet, hypertensive, hemorrhagic and edema inducing effects. In this study, the three dimensional structure of PLA(2) of Naja sputatrix (Malayan spitting cobra) was modeled by I-TASSER, SWISS-MODEL, PRIME and MODELLER programs. The best model was selected based on overall stereo-chemical quality. Further, molecular dynamics simulation was performed to know the stability of the modeled protein using Gromacs software. Average structure was generated during the simulation period of 10ns. High throughput virtual screening was employed through different databases (Asinex, Hit finder, Maybridge, TOSLab and ZINC databases) against PLA(2). The top seven compounds were selected based on the docking score and free energy binding calculations. These compounds were analyzed by quantum polarized ligand docking, induced fit docking and density functional theory calculation. Furthermore, the stability of lead molecules in the active site of PLA(2) was employed by MD simulation. The results show that selected lead molecules were highly stable in the active site of PLA(2).

• 出版日期2016-3-3