New visualization of dynamical flexibility of N-Glycans: Umbrella Visualization in UnityMol.

N-glycosylations play an important role in protein functions and some alterations of glycosylation such as sialic-acid hydrolysis are related to protein dysfunction. In vitro study of N-glycans can be a challenging task because of the structural diversity and the many reactive groups of the glycan chains. Molecular dynamics is a useful tool and probably the only one in biology able to overcome this problem and give access to conformational informations through exhaustive sampling. To better decipher the impact of N-glycans, we have to visualize their influence over time on the protein structure. This is why we recently developed a new 2D graphical method called the Umbrella Visualization to assess, as a density graph, the protein surface covered by glycans during a molecular dynamics trajectory. Whereas this methodology brought relevant informations related to the glycans intrinsic flexibility and dynamics, we needed further developments in order to integrate an accurate description of the protein topology and its interactions. We propose here to transform this analysis method into a visualization mode in UnityMol. UnityMol is a molecular editor, viewer and prototyping platform, coded in C# with the Unity3D game engine. The new representation of glycan chains presented in this study takes into account both the main positions adopted by each antenna of the glycan and the intensity of their motions. The adapted Umbrella Visualization provides invaluable informations about the protein surface shadowed by the glycan antennas. Ultimately, the analysis of the collected data allows us to discuss both the flexibility of the glycan (=ability to explore distinct areas), and its stability (= ability to avoid spreading from its main conformational state) and offers the possibility of identifying the key elements in the protein/glycan interactions.