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Prediction of organismal viability upon exposure to a nanoparticle in varying environments─as fully specified at the molecular scale─has emerged as a useful figure of merit in the design of engineered nanoparticles. We build on our earlier finding that a bag of artificial neural networks (ANNs) can provide such a prediction when such machines are trained with a relatively small data set (with ca. 200 examples). Therein, viabilities were predicted by consensus using the weighted means of the predictions from the bags. Here, we confirm the accuracy and precision of the prediction of nanoparticle viabilities using an optimized bag of ANNs over sets of data examples that had not previously been used in the training and validation process. We also introduce the viability strip, rather than a single value, as the prediction and construct it from the viability probability distribution of an ensemble of ANNs compatible with the data set. Specifically, the ensemble consists of the ANNs arising from subsets of the data set corresponding to different splittings between training and validation, and the different bags (k-folds). A k−1k machine uses a single partition (or bag) of k – 1 ANNs each trained on 1/k of the data to obtain a consensus prediction, and a k-bag machine quorum samples the k possible k−1k machines available for a given partition. We find that with increasing k in the k-bag or k−1k machines, the viability strips become more normally distributed and their predictions become more precise. Benchmark comparisons between ensembles of 4-bag machines and 34 fraction machines suggest that the 34 fraction machine has similar accuracy while overcoming some of the challenges arising from divergent ANNs in the 4-bag machines. 

The composition, orientation, and conformation of proteins in biomolecular coronas acquired by nanoparticles in biological media contribute to how they are identified by a cell. While numerous studies have investigated protein composition in biomolecular coronas, relatively little detail is known about how the nanoparticle surface influences the orientation and conformation of the proteins associated with them. We previously showed that the peripheral membrane protein cytochrome c adopts preferred poses relative to negatively charged MPA-AuNPs. Here, we employ molecular dynamics simulations and complementary experiments to establish that cytochrome c also assumes preferred poses upon association with nanoparticles functionalized with an uncharged ligand, and specifically ω-(1-mercaptounde-11-cyl)hexa(ethylene glycol) (EG6). We find that the display of the EG6 ligands is sensitive to the curvature of the surface—and consequently, the effective diameter of the nearly spherical nanoparticle core—which in turn affects the preferred poses of cytochrome c.