(304d) Enhanced Sampling of Protein Structures at the Air-Water Interface

Proteins at the air-water interface are of importance for several relevant biological and industrial purposes including the formation of biofilms and the production of foods containing large air bubbles. The unique way in which water orders itself at interfaces with air and the nature of air as a disordered hydrophobic medium cause proteins to exhibit large structural differences between solution and interfacial structures. One of the few experimental methods that provides information about the structure and orientation of proteins at the air-water interface is sum frequency generation spectroscopy (SFG). One shortcoming of SFG is that diverse structures can produce similar spectra. To overcome this challenge, molecular simulation can be utilized to provide an ensemble of structures that are likely present at the interface. In this study, we use well-tempered metadynamics to uncover the most probable structures of four model peptides at the air-water interface. Then, the spectra of these structures are calculated and compared to experiments. Several different protein and water force field combinations are examined to determine which model is most consistent with experiments. We find that CHARMM-family force fields prefer to remain near the solution structure while AMBER-family force fields exhibit much more conformational diversity. This information and the methods we develop can be used to guide future simulations of proteins at the air-water interface and to provide detailed structures that accurately represent SFG data.