Tubulin inhibitor SAR studies
Docking, molecular dynamics, and interaction analysis used to interpret experimental SAR for tubulin-targeting compound series.
Colchicine-BODIPY Probes: Evidence for the Involvement of Intracellular Membranes in the Targeting of Colchicine to Tubulin (ACS Pharmacol. Transl. Sci., 2025)Click estradiol dimers with novel aromatic bridging units: synthesis and anticancer evaluation (J. Enzyme Inhib. Med. Chem., 2024)Triazole-based estradiol dimers prepared via CuAAC from 17α-ethinyl estradiol with five-atom linkers causing G2/M arrest and tubulin inhibition (Bioorg. Chem., 2023)Anticancer 5-arylidene-2-(4-hydroxyphenyl)aminothiazol-4(5H)-ones as tubulin inhibitors (Arch. Pharm., 2022)
Scientific problem
Understanding the experimental SAR of tubulin-targeting compounds required a structural explanation of how linker composition and molecular modifications affect their binding and dynamics in the colchicine-binding site.
Motivation
The computational work was used to test plausible binding hypotheses and examine whether ligand dynamics, persistent contacts, and linker geometry could explain experimentally observed SAR.
My role
- Performed molecular docking, molecular dynamics simulations, trajectory analysis, and MM/PBSA calculations for tubulin–ligand complexes.
- Analyzed protein–ligand interactions with ProLIF and interpreted the results alongside experimental activity data.
- Parameterized boron-containing colchicine–BODIPY ligands using Gaussian-derived RESP charges.
- Co-author of four publications arising from these collaborations.
Methodology
- Collection and analysis of docking poses generated with AutoDock Vina.
- Explicit-solvent molecular dynamics simulations of selected complexes in GROMACS.
- RMSD and frame-wise protein–ligand interaction analysis with ProLIF, including water-bridge analysis.
- MM/PBSA calculations for selected compound series.
- Quantum-chemical derivation of partial charges for boron-containing ligands.
Results
- Co-author of 4 publications
Software
- GROMACS
- AmberTools
- AutoDock Vina
- ProLIF
- gmx_MMPBSA
- Gaussian
- RDKit
- PyMOL
- Chimera