| Predicting and controlling the biophysical chemistry of protein/host interactions remains a pressing challenge of high fundamental interest across many subfields in chemistry, engineering, and medicine. Our ability to (experimentally) probe interfacial interactions between a surface, polymer, or solvent and a biomolecule has increased due to high-resolution NMR and other spectroscopic techniques. However, new structural and mechanistic insights coming from experiments alone have been limited due to---in the case of the protein/liquid interface---the compounding challenges of simultaneously studying the protein/host interface and elucidating sequence specific interactions, and in the case of the protein/surface interface---the lack of a single unifying technique that can fully resolve the structure of an adsorbed protein. For the protein/liquid interface, the challenge is even worse in the case of synthetic frameworks such as ionic liquids (ILs) where the combinatorial design space of the solvent and protein sequence explodes beyond what could ever be feasibly considered in a laboratory. The field could be greatly advanced through the use of predictive, physics-based simulations; however, best practices of how to simulate protein interfacial adsorption and extract meaningful information about protein/host interactions from molecular simulations for direct experimental comparison, are still developing. Herein, we aim to address these challenges through the use of a variety of statistical enhanced sampling simulation techniques and novel analytical approaches. A number of systems are simulated, ranging from small model proteins adsorbing onto solid, idealized surfaces, to simulations of full proteins in complex solution environments. Ultimately, these simulations should lead to large improvements in the way we use computers to study multifaceted interfacial processes like protein adsorption, in addition to providing new fundamental insights into protein/host interactions. |
