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

Paulo, Siani; Khandelia, H.; Orsi, Mario; Dias, Luis G

Abstract

© 2018, Springer Nature Switzerland AG. 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.

• Journal Article Type: Article
• Acceptance Date: Sep 12, 2018
• Online Publication Date: Oct 26, 2018
• Publication Date: Nov 1, 2018
• Deposit Date: Oct 26, 2018
• Publicly Available Date: Oct 27, 2019
• Journal: Journal of Computer-Aided Molecular Design
• Print ISSN: 0920-654X
• Electronic ISSN: 1573-4951
• Publisher: Springer (part of Springer Nature)
• Peer Reviewed: Peer Reviewed
• Volume: 32
• Issue: 11
• Pages: 1259-1271
• DOI: https://doi.org/10.1007/s10822-018-0164-4
• Keywords: cholesterol, DPPC, coarse-grained, lipid bilayers, molecular dynamics, diffusion
• Public URL: https://uwe-repository.worktribe.com/output/857629
• Publisher URL: https://doi.org/10.1007/s10822-018-0164-4
• Related Public URLs: https://doi.org/10.1007/s10822-018-0164-4
• Additional Information: Additional Information : The final publication is available at Springer via https://doi.org/10.1007/s10822-018-0164-4.
• Contract Date: Oct 26, 2018