title: Interaction of a calix[4]arene derivative with a DOPC bilayer: biomolecular simulations towards chloride transport.
abstract: The ability of a calix[4]arene derivative (CX-1), bearing four protonated NH3(+) groups located in the upper rim and aliphatic tails in the lower rim, to interact with a 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) model bilayer and promote transmembrane chloride transport was investigated by molecular dynamics (MD) simulations. Unconstrained MD simulations show that the interaction of CX-1 with DOPC occurs via the NH3(+) groups, which are able to establish electrostatic interactions and multiple hydrogen bonds with the DOPC phosphate groups, while the aliphatic tails point towards the water phase (when CX-1 starts from the water phase) or to the membrane (when CX-1 is initially positioned within the bilayer). The interaction does not induce any relevant perturbation on the biophysical properties of the bilayer system (area per lipid, thickness, and hydration) apart from a systematic increase in the order parameter of the C2 carbon atom of the sn-1 lipid tail, meaning that the bilayer conserves its integrity. Since total internalization of CX-1 was not observed in the unconstrained MD time-scale, constant velocity steered molecular dynamics (SMD) simulations were performed in order to simulate the CX-1 permeation across the bilayer. At pulling velocities lower than 0.0075 nmps(-1), chloride transport was observed. The Potential of Mean Force (PMF), calculated with the weighted histogram analysis method, indicates a barrier of ca. 58kJmol(-1) for this mobile carrier to cross the membrane.
authors: Departamento de Química, CICECO and Secção Autónoma de Ciências da Saúde, Universidade de Aveiro, Aveiro 3810-193, Portugal.
authors: Paulo J
authors: PJ
authors: Costa
authors: Departamento de Química, CICECO and Secção Autónoma de Ciências da Saúde, Universidade de Aveiro, Aveiro 3810-193, Portugal.
authors: Igor
authors: I
authors: Marques
authors: Departamento de Química, CICECO and Secção Autónoma de Ciências da Saúde, Universidade de Aveiro, Aveiro 3810-193, Portugal. Electronic address: vitor.felix@ua.pt.
authors: Vítor
authors: V
authors: Félix
mesh_terms: D047250:Calixarenes / Q000737:chemistry / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D002712:Chlorides / Q000737:chemistry / Q000378:metabolism*; D017136:Ion Transport; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D010636:Phenols / Q000737:chemistry / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism*
chemical_list: D002712:Chlorides; D008051:Lipid Bilayers; D010636:Phenols; D010713:Phosphatidylcholines; C121325:calix(4)arene; D047250:Calixarenes; C017251:1,2-oleoylphosphatidylcholine
keywords: Calixarene; Carrier mechanism; DOPC; Molecular dynamics simulation; Transmembrane chloride transport