A molecular dynamics investigation of side-chain influence on the formation of A8-35 amphipol particles.

Abstract

We present all-atom molecular dynamics simulations of A8-35 amphipol, a polymer designed to stabilize the native conformation of membrane proteins in aqueous solution. These simulations were designed to reproduce the experimentally observed self-assembly of four A8-35 chains into a particle with an approximate molar mass of 40 kD as previously reported by Gohon et al. Comparison between the simulations and small angle neutron scattering confirms the nanometer scale structure of the particle. Using atomistic resolution, we have studied the polymers ability to form microdomains of like moieties, a feature with implications in the stabilization of membrane proteins. Using five distinct side-chain sequences, we observe different extents of side-chain self-association. An additional simulation describes the affect of a higher ionic concentration, which causes a dramatic reorganization of the particle, leading to increased side-chain self-association. Collectively, these simulations describe with atomistic detail the range of structures observed in a statistical polymerization, suggesting which features may be exploited for the improvement of membrane protein stabilization.