The symmetric difference distance: A new way to evaluate the evolution of interfaces along molecular dynamics trajectories; Application to influenza hemagglutinin

Abstract

We propose a new and easy approach to evaluate structural dissimilarities between frames issued from molecular dynamics, and we test this methodology on human hemagglutinin. This protein is responsible for the entry of the influenza virus into the host cell by endocytosis, and this virus causes seasonal epidemics of infectious disease, which can be estimated to result in hundreds of thousands of deaths each year around the world. We computed the three interfaces between the three protomers of the hemagglutinin H1 homotrimer (PDB code: 1RU7) for each of its conformations generated from molecular dynamics simulation. For each conformation, we considered the set of residues involved in the union of these three interfaces. The dissimilarity between each pair of conformations was measured with our new methodology, the symmetric difference distance between the associated set of residues. The main advantages of the full procedure are: (i) it is parameter free; (ii) no spatial alignment is needed and (iii) it is simple enough so that it can be implemented by a beginner in programming. It is shown to be a relevant tool to follow the evolution of the conformation along the molecular dynamics trajectories.