The evaluation of distribution and orientation for pochonin series of HSP90 inhibitors by molecular dynamics simulation at liquid/liquid interface

Heat shock protein 90 (Hsp90) takes part in the developments of several cancers. Pochonin class of HSP90 inhibitors will probably use as an important anticancer drug in the future. In this work, we explored the valuable structural information regard to pochonin derivatives based on molecular dynamics simulation at octanol/water interface. Oral bioavailability of drug candidates depends on the aqueous solubility of the compound. On the other hand, lipophilicity is a fundamental physicochemical property in drug discovery as it determines the extent of penetration of drugs into cells. Moreover, there is no known standard methodology that can efficiently evaluates solubility and permeability of drug candidates prior to their synthesis under biological conditions. The solubility and partitioning of a drug candidate from water into a bulk hydrophobic solvent is evaluated by using molecular dynamics simulation. Our results indicate that if drug candidate self-assembled at ocanol/water interface, it can be given orally. These surprising results may lead to novel routs for the development of new drugs. To obtain a deep understanding of the mechanism of the interfacial self-assembly, the orientation of these HSP90 inhibitors at different interfacial layers are analyzed.