Lili-Mip trajectories and results.zip

The unique viviparous Pacific Beetle cockroaches provide nutrition to their embryo by secreting milk proteins Lili-Mip, which is a lipid-binding glycoprotein that crystallizes in-vivo. The resolved in-vivo crystal structure of variably glycosylated Lili-Mip 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-Mip a very attractive model system to investigate the role of glycans on protein structure, dynamics, and function. Towards that end, we have employed all-atom molecular dynamics simulations on various glycosylated stages of a bound and free Lili-Mip protein and characterized 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 the nutrient storage function of the Lili-Mip protein. Our analyses show that the glycans stabilize spatially proximal residues and regulate the low amplitude opening motions of the residues at the entrance of the binding pocket. Glycans also preserve the native orientation and conformational flexibility of ligand. However, we find that extreme glycosylation with highly complex glycans or deglycosylation affects the conformation and dynamics noticeably. A simple but effective distance- and correlation-based network analyses of the protein also reveal the key residues regulating the architecture and ligand binding characteristics of the barrel in response to glycosylation.