Drug Design Studio (DDS) 4.0: A Nano-Pharmaceutical Platform for Modelling of Drug–Drug Complexation and Drug–Nanocarrier Encapsulation and Interactions

Once a candidate molecule has been designed, its therapeutic value in practice is often decided not by its intrinsic potency but by whether it can be formulated—dissolved, stabilised and delivered. Modern pharmaceutics addresses this with nanoscale carriers (cyclodextrins, dendrimers, polymeric nanoparticles, micelles, liposomes and carbon nanomaterials, etc.) and with carrier-free solid-form engineering such as pharmaceutical cocrystals. Predicting, before the bench, whether a given drug will associate with a chosen carrier, in what geometry, and through which specific interactions is therefore of central practical importance, yet it remains fragmented, and expertise-intensive: the researcher must generate three-dimensional conformers, place the guest into a host cavity or onto its surface, minimise the assembly with a molecular-mechanics force field that correctly retains inter-molecular terms, and most importantly analyse the different interaction forces and estimate the binding affinities and solvent effects—each step in a different tool and none accessible to a typical formulation scientist. Here, we present the Nano Bio-Pharmaceutical Modelling module of Drug Design Studio (DDS), an integrated platform that models both drug–nanocarrier and carrier-free drug–drug complexes in one interface. From a SMILES string and a built-in carrier library, DDS generates conformers, runs a deterministic, geometry-aware global search (regime-adaptive random-restart and basin-hopping Monte-Carlo-minimization), and reports an interaction energy decomposed into van der Waals, electrostatic and non-polar terms under a gas-phase or implicit-water model, with hydrogen-bond, hydrophobic and π-stacking profiles, 2D/3D interaction maps, and selectable stoichiometry and thoroughness tiers. We validate the module at two levels over twenty-nine complexes spanning four association regimes. First, mode reproduction: this recovers the experimentally established association geometry across all four regimes—cyclodextrin inclusion, dendrimer-surface complexation, carbon-nanomaterial adsorption and carrier-free drug–drug cocrystals. Second, quantitative agreement: across twelve α-, β- and γ-cyclodextrin inclusion complexes, the predicted implicit-water interaction energy correlates with the experimental binding free energy at Pearson r = 0.85 (p < 0.001; Spearman ρ = 0.73), rising from r = 0.73 in the gas phase—evidence that the implicit-solvent treatment captures the dominant energetic determinants of aqueous binding and tracks the experimental thermodynamic trend (a correlation and correct ranking). The Nano module shares one application and compute engine with the docking, covalent/non-covalent virtual-screening, network-pharmacology and QSAR modules of earlier DDS releases. DDS is publicly and freely accessible software for academic use.