Lili-Mip trajectories and results.zip

The unique viviparous Pacific Beetle cockroaches provide nutrition to their<br>embryo by secreting milk proteins Lili-Mip, which is a lipid-binding glycoprotein that crys-<br>tallizes in vivo. The resolved in vivo crystal structure of variably glycosylated Lili-Mip<br>shows a classical Lipocalin fold with an eight-stranded antiparallel beta-barrel enclosing a<br>fatty acid. The availability of physiologically unaltered glycoprotein structure makes Lili-<br>Mip a very attractive model system to investigate the role of glycans on protein structure,<br>dynamics, and function. Towards that end, we have employed all-atom molecular dynamics<br>simulations on various glycosylated stages of a bound and free Lili-Mip protein and charac-<br>terized the impact of glycans and the bound lipid on the dynamics of this glycoconjugate.<br>Our work provides important molecular-level mechanistic insights into the role of glycans in<br>the nutrient storage function of the Lili-Mip protein. Our analyses show that the glycans<br>locally stabilize spatially proximal residues and regulate the low amplitude opening motions<br>of the residues at the entrance of the binding pocket. Glycans, which are located at the<br>portal end of the barrel, also restrict the distal barrel depth and allosterically modulate<br>the lipid dynamics in the barrel. A simple but effective distance-based network analysis<br>of the protein also reveals the role of glycans in the subtle rewiring of residues crucial for<br>determining the barrel depth and lipid orientation