Combining spectroscopy experiments and molecular simulation to determine structural and mechanistic details of adsorbed biomolecules
Kayla Sprenger1, Tobias Weidner2, Jim Pfaendtner1
1Department of Chemical Engineering, University of Washington, Seattle, WA, 98195, USA
2Max Planck Institute for Polymer Research, Mainz, 55128, Germany
Proteins and the mechanisms they mediate at solid/liquid interfaces play a critical role in many processes including surface fouling, biocatalysis, and biomineralization. Despite their importance, we often lack a molecularly detailed understanding of interfacial mechanisms such as protein recognition, binding, and surface-induced conformational change. While atomistic simulations of protein adsorption have strong potential to combine with experiments to elucidate structural and mechanistic details at the interface, challenges of timescale limitations and strong protein/surface binding have prohibited the progress of such simulations. To-date there are virtually zero structures of a biomolecule adsorbed to a surface that have been made accessible in the Protein Data Bank. For the first time results of molecular simulation, using the enhanced sampling method PTMetaD-WTE1 to overcome aforementioned challenges, have been combined with experimental data from solid-state nuclear magnetic resonance (ssNMR), near edge X-ray adsorption fine structure (NEXAFS), and sum frequency generation spectroscopy (SFG) to determine the structure and orientation of the SN15 binding domain of the salivary protein statherin on hydroxyapatite (HAp). Additionally, multiple SN15 peptides have been simulated to represent more closely the experimental conditions of a crowded microenvironment at the interface. Resulting structural information is compared to the single protein adsorption results to determine the role of lateral protein-protein interactions. From this comparison, mechanistic details of statherin film formation and its control of HAp growth are hypothesized. This poster will also propose some general principles for efficiently simulating with metadynamics and computing experimental observables for protein adsorption systems.
 Deighan, M.; Bonomi, M.; Pfaendtner, J. Efficient Simulation of Explicitly Solvated Proteins in the Well-Tempered Ensemble. JCTC 2012, 8, 2189-2192.
See more of this Group/Topical: Computational Molecular Science and Engineering Forum