Polarizable atomic multipole-based force field for cholesterol

Abstract

Cholesterol is one of the essential component of lipid in membrane. We present a polarizable atomic multipole force field (FF) for the molecular dynamic simulation of cholesterol. The FF building process follows the computational framework as the atomic multipole optimized energetics for biomolecular applications (AMOEBA) model. In this framework, the electronics parameters, including atomic monopole moments, dipole moments, and quadrupole moments calculated from ab initio calculations in the gas phase, are applied to represent the charge distribution. Furthermore, the many-body polarization is modeled by following the same pattern of distributed atomic polarizabilities. Then, the bilayers composed of two typical phospholipid molecules, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), in a range of different cholesterol concentrations are built and implemented by molecular dynamics (MD) simulations based on the proposed polarizable FF. The simulation results are statistically analyzed to validate the feasibility of the proposed FF. The structural properties of the bilayers are calculated to compare with the related experimental values. The MD values show the same trend of experimental values changes. Communicated by Ramaswamy H. Sarma