Parameterization of a coarse-grained model of cholesterol with point- dipole electrostatics

P Siani and H Khandelia and M Orsi and LG Dias, JOURNAL OF COMPUTER- AIDED MOLECULAR DESIGN, 32, 1259-1271 (2018).

DOI: 10.1007/s10822-018-0164-4

We present a new coarse-grained (CG) model of cholesterol (CHOL) for the electrostatic-based ELBA force field. A distinguishing feature of our CHOL model is that the electrostatics is modeled by an explicit point dipole which interacts through an ideal vacuum permittivity. The CHOL model parameters were optimized in a systematic fashion, reproducing the electrostatic and nonpolar partitioning free energies of CHOL in lipid/water mixtures predicted by full-detailed atomistic molecular dynamics simulations. The CHOL model has been validated by comparison to structural, dynamic and thermodynamic properties with experimental and atomistic simulation reference data. The simulation of binary DPPC/cholesterol mixtures covering the relevant biological content of CHOL in mammalian membranes is shown to correctly predict the main lipid behavior as observed experimentally.

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