A Molecular Dynamics Simulation Study of the P44 Mutant of Bovine R-Arrestin

Veronica Slootsky
University of Maryland, Baltimore County

P44 is the splice variant of bovine visual R-arrestin and naturally occurs in the Rod Outer Segment at a ratio of 1:10 the concentration of R-arrestin (ShrÖder et. all). The biochemical function of this variant is still undefined. Our work addresses this issue, from a computational prospective. This variant protein has an identical amino acid sequence to the visual R-arrestin except that the last 35 residues on the C-terminal have been replaced by a single alanine. A starting (hypothetical) structure of the P44 variant is proposed and is based on the wild-type R-arrestin crystal structure (Hirsch, 1999). The P44 variant of R-arrestin is subsequently studied in solution using highly parallel Molecular Dynamics simulations. By utilizing the CHARMM force field (MacKerell, 1998) in conjunction with the package NAMD, the structure and stability of this protein variant is studied in solution. Our simulations include all-atoms of the protein and explicit waters, for complete solvation. The system is equilibrated for 1 ns and thereafter up to 10 ns of simulation dynamics are preformed. By an analysis of the trajectories for structural differences between the R-arrestin and the P44 variant, a three-dimensional model of the P44 protein is proposed.