In this project, BioSolveIT 's tools will be used for chemical modifications of 2-hexadecynoic acid (2-HDA) againts FabI enzyme from the multidrug resistant S.aureus. The main goal is to obtain hits for the development of new protential antibiotics. Our workflow is to use 2-HDA as a scaffold to investigate potential improvements in binding energies and affinity against FabI. Docking simulations and structural modifications will be performed using SeeSAR's features such as Molecule Editor and Inspirator Modes which can directly modify ligands, then run MedChemesis, and receive immediate visual feedback on binding affinity. These findings will show the capability of structure-based ligand modification, using BioSolveIT software, as a strategy for designing effective inhibitors targeting FabI, contributing to ongoing efforts to address antibiotic resistance.
Christina intends to achieve the following milestones:
- Identify binding pockets in FABI (PDB: 4ALM) and analyze druggability.
- Scafold based design using 2-HDA. Explore variations and generate analogs. Create library and proceed docking to FabI
- Post docking analysis and prioritization of candidates. Predict ADMET properties. Select top hit.