Helicobacter pylori infection is a major public health problem linked to gastric cancer and antibiotic resistance. This project designs novel multi-target inhibitors from 857 secondary metabolites of 15 Peruvian medicinal plants, targeting urease, the protease HtrA, and shikimate kinase. Libraries will be prepared using CoLibri and pooled using FTrees. Flexible molecular docking and thermodynamic evaluation will be performed using FlexX, SeeSAR, and HYDE. To optimize structural cores through multiple substitutions, combinatorial chemical spaces will be explored using FTrees-FS and SpaceMACS, followed by high-throughput virtual screening using HPSee. Finally, the main derivatives will undergo quantum-mechanical validation (DFT in ORCA), molecular dynamics simulations (GROMACS), and gmx_MMPBSA analysis to confirm conformational stability and binding free energy. This workflow seeks to accelerate the discovery of new anti-H. pylori candidates derived from Peruvian biodiversity.
Andrey Justin intends to achieve the following milestones:
- Library preparation via CoLibri/FTrees and flexible molecular docking with FlexX/SeeSAR to identify initial hits against the three targets.
- Scaffold optimization of selected hits using ReCore/infiniSee and electronic validation with DFT in ORCA.
- Molecular Dynamics simulations in GROMACS and gmx_MMPBSA to determine final ligand stability and binding energy.