Method to Construct Volcano Relations by Multiscale Modeling: Building Bridges between the Catalysis and Biosimulation Communities

Understanding the complex interactions of different building blocks within a sophisticated drug-delivery system (DDS), aimed at targeted transport of the drug to malignant cells, requires modeling techniques on different time and length scales. On the example of the anthracycline antibiotic doxorubicin (DOX), we investigate a potential DDS component, consisting of a gold nanoparticle and a short peptide sequence as carriers of DOX. The combination of atomistic molecular dynamics simulations and density functional theory calculations facilitates compiling a volcano plot, which allows deriving general conclusions on DDS constituents for chemotherapeutic agents within the class of anthracycline antibiotics: the nanoparticle and peptide carrier moieties need to be chosen in such a way that the anthracycline body of the drug is able to intercalate between both entities or between two (π-stacking) residues of the peptide. Using the popular volcano framework as a guideline, the present article connects the catalysis and biosimulation communities, thereby identifying a strategy to overcome the limiting volcano relation by tuning the coordination number of the drug in the DDS component.