Molecular Modeling of Phospholamban
EMSL Project ID
2637
Abstract
The primary aim of this project is to use molecular modeling to gain a better understanding of the structure and dynamics of phospholamban (PLB). Phospholamban is a transmembrane protein of 52 amino acids. PLB regulates the calcium ATPase of the cardiac sarcosplasmic reticulum through an inhibitory association that can be reversed by phosphorylation. The proposed studies will begin with molecular dynamics simulations of PLB in methanol solution, starting from the recently determined NMR structure. Further simulations will be performed in water, to study the effects of the environment on PLB structure, and in a lipid bilayer to model behavior in the membrane environment. PLB variants with phosphorylated Ser 16 and Thr 17 will also be simulated to study the effect of phosphorylation on the protein structure. Overall, our simulations will yield an improved understanding of the structure and dynamics of phospholamban, and of changes induced by variation in external environment and by phosphorylation. The long-range goal is to help explain the microscopic mechanism of regulation of the calcium ATPase by PLB. This regulation is responsible for the cyclic changes in the calcium level that accompany normal heart function, while disruption of calcium level regulation is associated with various disease states. The simulations will be performed using the program CHARMM. The project requires the use of fast parallel supercomputers to generate several trajectories of the solvated protein of several nanosecond length.
Project Details
Project type
Exploratory Research
Start Date
2002-10-01
End Date
2003-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members