COMPUTATIONAL STUDY OF MEMBRANE / PROTEIN INTERACTION

Almost half a million Americans die of cardiac arrhythmias following a myocardial infarction (heart attack) every year, according to the American Heart Association. Arrhythmias are a consequence of the functional remodeling of ionic channels and gap junctional proteins that follow a myocardial infarction. Ionic channels are proteins embedded in the cell membrane. Our overall hypothesis is that changes in cell membrane lipid composition alter the function of ionic channel proteins.  We will use molecular dynamics computer simulations to quantify the equilibrating interactions between the ionic channel and the lipid molecules in the cell membrane.  We will test our hypothesis by evaluating the effects of changes in membrane lipid composition on the functional properties of hERG potassium protein channel ([hERGPO]. First, we will develop molecular based computer models consisting a hERGPO embedded in membranes with different lipid compositions. Second, we will use those computer models to evaluate the energy profiles along the ion channel pore and determine the effects of membrane lipid composition on channel permeability.  In this talk, we will present the use Nanoscale Molecular Dynamics (NAMD) to study ion channel/cell membrane molecular interactions, in a model consisting of the hERG channel embedded in a membrane with the lipid composition of rat myocytes. The simulation results explain the selectivity of hERG for K⁺ over Na⁺.