Glycosylation and Crowded Membrane Effects on Influenza Neuraminidase Stability and Dynamics

Abstract

All protein simulations are conducted with varying degrees of simplifications, oftentimes with unknown ramifications on how these simplifications affect the interpretability of the results. In this work we investigated how protein glycosylation and lateral crowding effects modulate an array of properties characterizing the stability and dynamics of influenza neuraminidase. We constructed three systems: 1) Glycosylated neuraminidase in a whole virion (i.e. crowded membrane) environment 2) Glycosylated neuraminidase in its own lipid bilayer 3) Unglycosylated neuraminidase in its own lipid bilayer. We saw that glycans tend to stabilize the protein structure and reduce its conformational flexibility while restricting solvent movement. Conversely, a crowded membrane environment encouraged exploration of the free energy landscape and a large scale conformational change while making the protein structure more compact. Understanding these effects informs what factors one must consider while attempting to recapture the desired level of physical accuracy. TOC figure O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=50 SRC="FIGDIR/small/556910v2_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@ec7a9org.highwire.dtl.DTLVardef@563495org.highwire.dtl.DTLVardef@1965cd7org.highwire.dtl.DTLVardef@a9659d_HPS_FORMAT_FIGEXP M_FIG TOC. Schematic of the three systems used here. (A) 2009-H1N1-ungly is the unglycosylated, single protein NA system. (B) 2009-H1N1-gly is the glycosylated, single protein NA system. (C) 2009-H1N1-vir is the NA in the virion context. C_FIG