We are using computational modeling techniques to build proteins that interact with biologically relevant targets (proteins, receptors, transporters, ion channels etc.). Specifically for this project we plan to target transferrin receptor as a way to boost exposure of therapeutics across the blood–brain barrier (BBB). The receptor is a multidomain protein anchored in the BBB membrane involved in the physiological facilitation of iron uptake. Here I will develop protein carriers for transferrin receptor-mediated passage of the BBB by using computational protein design. Protein structures will be built from fragments, amino acid conformations will be sampled by rotamer search, and atom positions will be minimized w.r.t. a force field. We plan on generating millions of structures for efficient conformational sampling.
The long-term goal is to couple therapeutics — as for example drugs against Alzheimer’s — to the designed carriers to increase the brain uptake and cure neurological disorders.
The allocated resources last year 20kh/month were not sufficient and we had to switch our calculations to collaborators. Our lab has expanded which leads us to higher allocation request for this round of application.