Cardiolipin Models for Molecular Simulations of Bacterial and Mitochondrial Membranes

Present in bacterial and mitochondrial membranes, cardiolipins have a unique dimeric structure, which carries up to two charges (i.e., one per phosphate group) and, under physiological conditions, can be unprotonated or singly protonated. Exhaustive models and characterization of cardiolipins are to date scarce; therefore we propose an ab initio parametrization of cardiolipin species for molecular simulation consistent with commonly used force fields. Molecular dynamics simulations using these models indicate a protonation dependent lipid packing. A peculiar interaction with solvating mono- and divalent cations is also observed. The proposed models will contribute to the study of the assembly of more realistic bacterial and mitochondrial membranes and the investigation of the role of cardiolipins for the biophysical and biochemical properties of membranes and membrane-embedded proteins.