Parameters for Martini sterols and hopanoids based on a virtual-site description

Abstract

Sterols play an essential role in modulating bilayer structure and dynamics. Coarse-grained molecular dynamics parameters for cholesterol and related molecules are available for the Martini force field and have been successfully used in multiple lipid bilayer studies. In this work, we focus on the use of virtual sites as a means of increasing the stability of cholesterol and cholesterol-like structures. We improve and extend the Martini parameterization of sterols in four different ways: 1 - the cholesterol parameters were adapted to make use of virtual interaction sites, which markedly improves numerical stability; 2 - cholesterol parameters were also modified to address reported shortcomings in reproducing correct lipid phase behavior in mixed membranes; 3 - parameters for ergosterol were created and adapted from cholesterols; and 4 - parameters for the hopanoid class of bacterial polycyclic molecules were created, namely, for hopane, diploptene, bacteriohopanetetrol, and for their polycyclic base structure.