Molecular design of anticancer drugs from marine fungi derivatives.
Duc Tuan CaoThi Mai Huong DoanVan Cuong PhamThi Hong Minh LeJung-Woo ChaeHwi-Yeol YunMin-Kyun NaYoung-Ho KimPham Minh QuanVan Hung NguyenPublished in: RSC advances (2021)
Heat shock protein 90 (Hsp90) is one of the most potential targets in cancer therapy. We have demonstrated using a combination of molecular docking and fast pulling of ligand (FPL) simulations that marine fungi derivatives can be possible inhibitors, preventing the biological activity of Hsp90. The computational approaches were validated and compared with previous experiments. Based on the benchmark of available inhibitors of Hsp90, the GOLD docking package using the ChemPLP scoring function was found to be superior over both Autodock Vina and Autodock4 in the preliminary estimation of the ligand-binding affinity and binding pose with the Pearson correlation, R = -0.62. Moreover, FPL calculations were also indicated as a suitable approach to refine docking simulations with a correlation coefficient with the experimental data of R = -0.81. Therefore, the binding affinity of marine fungi derivatives to Hsp90 was evaluated. Docking and FPL calculations suggest that five compounds including 23, 40, 46, 48, and 52 are highly potent inhibitors for Hsp90. The obtained results enhance cancer therapy research.
Keyphrases
- heat shock protein
- molecular dynamics
- molecular dynamics simulations
- molecular docking
- cancer therapy
- heat shock
- density functional theory
- drug delivery
- heat stress
- protein protein
- monte carlo
- structure activity relationship
- magnetic resonance
- big data
- risk assessment
- electronic health record
- transcription factor
- small molecule
- artificial intelligence
- diffusion weighted imaging
- contrast enhanced
- drug induced