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Biophysics of Proteins at Surfaces: Assembly, Activation, Signaling
Wednesday Speaker Abstracts
Ubiquitin Adsorbs on the TiO
2
(100) Surface by an Anchor-Lock Mechanism
Erik G. Brandt
, Alexander P. Lyubartsev.
Stockholm University, Stockholm, Sweden.
Proteins that unfold from their native states when adsorbed to inorganic surfaces can potentially
cause neurodegenerative diseases, including Parkinson's and Alzheimer's disease. Conversely,
proteins that retain their folded state when adsorbed to inorganic surfaces can act as favorable
binding sites to other biomolecules, depending on orientation and whether that orientation stays
fixed. When no unfolding occurs, the surface-adsorbed protein structure can be described by a
translation and subsequent rotation of the native folded state. We used atomistic and coarse-
grained molecular dynamics simulations to analyze the adsorption of ubiquitin – one of the most
common proteins in living organisms – to the fully hydrated TiO
2
(100) surface – one of the
most common engineered nanoparticle surfaces. Our simulations show that ubiquitin is a rigid
body during the adsorption process. We extracted the orientation angles for ubiquitin from the
optimal rigid body rotation matrix with regard to a known reference structure. The analysis
revealed that the tail of ubiquitin acts as an "anchor" for the otherwise rigid protein, and attaches
to the first solvation layer at the TiO
2
surface. The protein can rapidly "lock" into its preferred
adsorbed orientation once the anchoring is complete. The atomistic results were in agreement
with the full map of adsorbed orientations determined from coarse-grained modeling of TiO
2
-
protein interactions. The simulations emphasize the importance of strongly bound surface waters
for the adsorption behavior of solvated proteins at polar interfaces.