High performance, robust control of flexible space structures

Ph.D.Anthony J. Calis

Simulation-based prediction of phosphatidylinositol 4,5-Bisphosphate binding to an ion channel

Protein–lipid interactions regulate many membrane protein functions. Using a multi–scale approach which combines coarse–grained and atomistic molecular dynamics simulations we have predicted the binding site for the anionic phospholipid phosphatidylinositol 4,5–bisphosphate (PIP(2)) on the Kir2.2 inwardly–rectifying (Kir) potassium channel. Comparison of the predicted binding site to that observed in the recent PIP(2)–bound crystal structure of Kir2.2 reveals good agreement between simulation and experiment. In addition to providing insight into the mechanism by which PIP(2) binds to Kir2.2, these results help to establish the validity of this multi–scale simulation approach and its future application to examine novel membrane protein/lipid interactions in the increasing number of high–resolution membrane protein structures that are now available