Simulation of Trp-cage Mini-protein Dynamics at Multiple Temperatures

Current synthetic methods have allowed the production of fluorine containing analogs of common amino acids and thus proteins.  Because the Fluorine-19 nucleus has a spin of 1⁄2, the technology used in getting fluorine NMR data is very similar to proton NMR technology.  This unique approach has allowed for measuring the environment of a fluorine atom in a specific protein residue without worrying about overlapping of peaks from other residues.  Thus, fluorine NMR is useful in studying protein folding and ligand binding.  Yet the cause of shifts in fluorine NMR peaks at the atomic level are still unknown.  By studying the environment of an unmodified tryptophan residue in the trp-cage miniprotein, we hope to model the environment that a fluorine atom in a modified tryptophan would find itself in the majority of the time.  We hope to find a correspondence between NMR experiments and molecular modeling using molecular dynamics (MD) under the same conditions. 

First, we obtained the structure of the trp-cage miniprotein from the on-line Protein Data Bank.  To make sure the sample protein was in a relaxed state, we slowly equilibrated it to the respective test temperatures: 283K, 293K, 303K.  For each of the three simulations we utilized the AMBER modeling program to calculate the dynamics of the protein over twenty nanoseconds.  After these MD trajectories were finished, we compiled results on each and compared them.  We specifically looked at the environment of the tryptophan residue and how it differed in the various temperatures.  We considered both average properties and deviations between the MD trajectories. 

The ultimate goal of this research is to directly compare the data from the fluorine NMR with the data we gathered from the molecular dynamics.