We’re excited to share some recent results from our lab that combine simulation and experimental structural biology. This has been a wonderful collaboration with my colleague Linda Columbus, a Chemistry professor at the University of Virginia. We are interested in how Neisseria bacteria recognize and infect cells. This is an important problem #1 because Neisseria are becoming increasingly drug-resistance and #2 because these mechanisms can be borrowed for targeted drug delivery. Neisseria use a set of proteins called “Opa proteins” on their surface to bind to cells and get inside. The structure of these proteins is very interesting–the part that sits in the membrane is well-structured, but the part that actually performs recognition is very flexible. When Prof. Columbus started studying these using NMR spectroscopy (a way to determine molecular structure), the data she got on the recognition end of the protein wasn’t enough to uniquely determine the structure. My lab and hers partnered to perform molecular simulations of Opa proteins–the recognition part of the protein is indeed flexible, but we were able to use molecular simulation and NMR together to define a bit better how the flexibility works and how it might be related to Opa’s function. Part of why Opa is so flexible is that it must on the one hand bind to cell receptors but on the other vary enough to evade the human immune response. We have a theory for what the Opa-cell receptor recognition complex might look like, and we are together performing more simulations and experiments to test this.
The work was published this summer in the Journal of the American Chemical Society: http://pubs.acs.org/doi/abs/10.1021/ja503093y