Research paperSpontaneous assembly of HSP90 inhibitors at water/octanol interface: A molecular dynamics simulation study

•Solubility and permeability of drug candidates were simulated at water/octanol interface.•It is observed that orally active HSP90 inhibitors form aggregates at the water/octanol interface.•The orientation of HSP90 inhibitors at different interfacial layers are analyzed.•This is a significant achievement of pharmaceutical application of liquid-liquid interfaces.

Drug absorption at an acceptable dose depends on the pair of solubility and permeability. There are many potent therapeutics that are not active in vivo, presumably due to the lack of capability to cross the cell membrane. Molecular dynamics simulation of radicicol, diol-radicicol, cyclopropane-radicicol and 17-DMAG were performed at water/octanol interface to suggest interfacial activity as a physico-chemical characteristic of these heat shock protein 90 (HSP90) inhibitors. We have observed that orally active HSP90 inhibitors form aggregates at the water/octanol and DPPC-lipid/water interfaces by starting from an initial configuration with HSP90 inhibitors embedded in the water matrix.

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