The performance and developability of biomolecular therapeutics are strongly influenced by higher-order structure, conformational dynamics, and solvent accessibility at the atomic scale. Yet many pharmaceutical attributes of interest— stability, aggregation propensity, and sensitivity to formulation or environmental changes—are still assessed using measurements that provide limited mechanistic insight into the underlying molecular behavior.

This research opportunity aims to establish a measurement framework that directly links atom-resolved protein dynamics and surface accessibility to macroscopic properties relevant to biotherapeutic development, formulation, and performance in biologically relevant environments. The central hypothesis is that quantitative, site-specific measurements of molecular motion and solvent exposure provide predictive indicators of how protein therapeutics respond to chemical, physical, and biological perturbations. Research efforts are expected to be driven primarily by nuclear magnetic resonance (NMR) measurements, complemented by orthogonal analytical techniques where appropriate to contextualize and validate atomic-scale observables.

These approaches will enable comparison of atomic-level dynamics across biotherapeutic systems, assessment of formulation effects, and detection of subtle structural or dynamic changes that precede loss of stability or function. By correlating higher-level quality assessments with atomic-scale dynamics measurements, this effort seeks to advance predictive capabilities beyond empirical screening toward mechanism-informed evaluation.

Overall, research proposals supported under this opportunity will advance new measurement strategies and datasets centered on NMR-derived, atom-resolved dynamics, enabling the development of models predictive of pharmaceutical quality attributes at the macroscopic level.