High-affinity selective inhibitor against phospholipase A2 (PLA2): a computational study.
Sathishkumar Chinnasamy1, Selvakkumar Chinnasamy2, Karthikeyan Muthusamy1
1a Department of Bioinformatics , Alagappa University , Karaikudi , Tamil Nadu , India and.
Journal of Receptor and Signal Transduction Research
|October 1, 2015
Summary
Researchers modeled the three-dimensional structure of Malayan spitting cobra phospholipase A2 (PLA2) and identified stable lead compounds. These findings advance understanding of PLA2
Area of Science:
- Biochemistry
- Structural Biology
- Pharmacology
Background:
- Phospholipase A2 (PLA2) is a key component of snake venom.
- PLA2 exhibits diverse toxicological and pharmacological effects, including neurotoxicity, myotoxicity, and cardiotoxicity.
Purpose of the Study:
- To model the 3D structure of Naja sputatrix PLA2.
- To identify potential drug candidates that can bind to and stabilize PLA2.
Main Methods:
- Protein structure modeling using I-TASSER, SWISS-MODEL, PRIME, and MODELLER.
- Molecular dynamics simulations with Gromacs.
- High-throughput virtual screening against multiple compound databases.
- Docking studies (QPLD, IFD) and DFT calculations.
- Stability analysis of lead compounds via MD simulations.
Main Results:
- A stable 3D model of Naja sputatrix PLA2 was generated.
- Seven lead compounds were identified through virtual screening and docking.
- Molecular dynamics simulations confirmed the high stability of these lead compounds within the PLA2 active site.
Conclusions:
- The study successfully modeled Naja sputatrix PLA2 and identified stable inhibitors.
- These findings provide a foundation for developing novel therapeutics targeting PLA2 activity.
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