Short Report by Sarina Rudolf: Incorporating crosslinking data into Rosetta to dock NPY and Y5R . (Oct. – Dec. 2019)
In the recent years, we pursued the goal to map the binding site of the ligand NPY at human neuropeptide Y5 receptor (Y5R). Therefore, we applied an approach called genetic code expansion to incorporate a photoreactive amino acid at a desired site at the extracellular part of the receptor. The obtained photocrosslinking-data revealed the proximity of several receptor positions to NPY in the ligand-receptor complex. Hence, giving us deeper insights into the receptor-binding pocket.
For the visualization of my experimental data in a comparative model, I got the opportunity to perform the computational modeling in the laboratories of Jens Meiler at the Vanderbilt University in Nashville, Tennessee. In the course of my exchange, I was introduced to the operating system Linux and shell programming.
The construction of the comparative Y5R model and the subsequently docking of NPY into the receptor-binding pocket was performed with the software Rosetta. Therefore, tutorials provided by the Rosetta Community supported my work.
The modelling of the Y5R turned out to be difficult by two different strategies due to its long intracellular loop 3. Nevertheless, comparative models of NPY docked into the Y5R binding pocket could be obtained, which will guide my research in the future.
During my exchange, I explored the sunny and musical city Nashville – either by myself or together with my fellows from the MeilerLab. Nashville is a beautiful city, which offers a lot of entertainment like concerts, sport-events or bar-hopping, which are accompanied by the Southern State kindness of Nashville’s citizen. It was interesting for me to learn about the American lifestyle and I enjoyed staying in Nashville as well as at the Vanderbilt University very much.