Accelerated Materials Discovery Using Chemical Informatics Investigation of Polymer Physicochemical Properties and...

Quantitative approaches to structure-property relationships are critical for the accelerated design and discovery of biomaterials in biotechnology and medicine. However, the absence of definitive structures, unlike those available for small molecules or 3D crystal structures available for some proteins, has limited the development of Quantitative Structure-Property Relationship (QSPR) models for investigating physicochemical properties and biological activity of polymers. In this study, we describe a combined experimental and cheminformatics paradigm for first developing QSPR models of polymer physicochemical properties, including molecular weight, hydrophobicity, and DNA-binding activity. Quantitative Structure-Activity Relationship (QSAR) models of polymer-mediated transgene expression were then developed using these physicochemical properties with an eye towards developing a novel two-step chemical informatics paradigm for determining biological activity (e.g., transgene expression) of polymer properties as related to physicochemical properties. We also investigated a more conventional approach in which biomaterial efficacy, i.e., transgene expression activity, was directly correlated to structural representations of the polymers used for delivering plasmid DNA. Our generalized chemical informatics approach can accelerate the discovery of polymeric biomaterials for several applications in biotechnology and medicine, including in nucleic acid delivery.