title: Simulation-based prediction of phosphatidylinositol 4,5-bisphosphate binding to an ion channel.
abstract: Protein-lipid interactions regulate many membrane protein functions. Using a multiscale approach that 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 multiscale simulation approach and its future application in the examination of novel membrane protein-lipid interactions in the increasing number of high-resolution membrane protein structures that are now available.
authors.affiliation: Department of Biochemistry,  University of Oxford , Oxford OX1 3QU, United Kingdom.
authors.forename: Matthias R
authors.initials: MR
authors.lastname: Schmidt
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Stansfeld
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Tucker
authors.forename: Mark S P
authors.initials: MS
authors.lastname: Sansom
mesh_terms: D000818:Animals; D001665:Binding Sites; D002645:Chickens; D056004:Molecular Dynamics Simulation; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding
chemical_list: C489463:Kir2.2 channel; D019269:Phosphatidylinositol 4,5-Diphosphate; D024661:Potassium Channels, Inwardly Rectifying