Determining the Diffusion Coefficient of Alpha-Factor Ligand in Water using Molecular Dynamics Simulations
Mentor 1
Valerica Raicu
Mentor 2
Mike Stoneman
Location
Union Wisconsin Room
Start Date
29-4-2016 1:30 PM
End Date
29-4-2016 3:30 PM
Description
The sterile two alpha factor receptor (Ste2) is a member of a group of proteins called G Protein Coupled Receptors (GPCRS). Together, GPCRs make up one of the largest families of cell-surface receptors, and thereby are involved in a wide range of biological functions. GPCRs also are targets of many clinically important drugs. A recent discover in our lab shows that GPCR pheromones can activate their corresponding GPCRs by crossing the cell membrane. Because numerous discoveries regarding the properties of Ste2 have shed light on the functions of GPCRs in general, we have studied the propensity of the Ste2 pheromone, i.e. the alpha–factor ligand, to penetrate the plasma membrane of a yeast cells. As part of this study, we needed to quantify the ligand’s diffusion in an aqueous medium. By using the open source molecular dynamics simulation software GROMACS, we tracked the positions and velocities of the alpha-factor atoms diffusing in water. Every 500 picoseconds, the positions and velocities of the atoms of the alpha-factor were calculated and stored. From the recorded position coordinates, we then calculated the mean square displacement (MSD) of the ligand’s center of mass as a function of time (time interval of 100 nanoseconds). The slope of the MSD vs time curve was then used to determine the diffusion coefficient of the ligand which was found to be 0.0039nm2/ps. Future simulations will (i) further refine this value (ii) and calculate the value in different types of cell media. The results of these simulations will be combined with fluorescence measurements tracking the amount of ligand crossing the cell membrane, leading to a better understanding of the possible pathways for not only Ste2 activation, but GPCRs in general.
Determining the Diffusion Coefficient of Alpha-Factor Ligand in Water using Molecular Dynamics Simulations
Union Wisconsin Room
The sterile two alpha factor receptor (Ste2) is a member of a group of proteins called G Protein Coupled Receptors (GPCRS). Together, GPCRs make up one of the largest families of cell-surface receptors, and thereby are involved in a wide range of biological functions. GPCRs also are targets of many clinically important drugs. A recent discover in our lab shows that GPCR pheromones can activate their corresponding GPCRs by crossing the cell membrane. Because numerous discoveries regarding the properties of Ste2 have shed light on the functions of GPCRs in general, we have studied the propensity of the Ste2 pheromone, i.e. the alpha–factor ligand, to penetrate the plasma membrane of a yeast cells. As part of this study, we needed to quantify the ligand’s diffusion in an aqueous medium. By using the open source molecular dynamics simulation software GROMACS, we tracked the positions and velocities of the alpha-factor atoms diffusing in water. Every 500 picoseconds, the positions and velocities of the atoms of the alpha-factor were calculated and stored. From the recorded position coordinates, we then calculated the mean square displacement (MSD) of the ligand’s center of mass as a function of time (time interval of 100 nanoseconds). The slope of the MSD vs time curve was then used to determine the diffusion coefficient of the ligand which was found to be 0.0039nm2/ps. Future simulations will (i) further refine this value (ii) and calculate the value in different types of cell media. The results of these simulations will be combined with fluorescence measurements tracking the amount of ligand crossing the cell membrane, leading to a better understanding of the possible pathways for not only Ste2 activation, but GPCRs in general.
