Our computational structural biology studies are geared towards obtaining deep, atom-level insight of chemically engineered post-translational modifications of trophic factor molecules.
These studies incorporate the results of mass spectrometry-based peptide mapping to develop a close understanding of ligand-receptor interactions. One of our goals is to utilize this information to design genetically engineered trophic factors with unique functional activity. We are also interested in designing small molecules by using available glutamate receptor crystal structure information. This work is primarily performed on a custom built multiprocessor HP Xeon workstation supporting true hardware 3D. We utilize a variety of software packages, with lab subscriptions to Yasara, Schrodinger suite, MOE, and PyMol.
Molecular dynamics simulations, shown above, were performed using Molecular Operating Environment software to obtain atom-level insight into ligand-receptors interactions. The three videos above are examples of molecular dynamics simulations of erythropoietin (EPO), a pleiotropic cytokine widely known for its role in elevating levels of red blood cell. The video with EPO side chains in green is the naturally occurring molecule. In blue side chains is a recombinant mutant, and in yellow is a naturally occurring mutant that results in anemia. At 5 seconds the video zooms in on the major active site of the protein-receptor complex, Active Site 1, which is the main focus of the simulation.