Reconstructing Potentials of Mean Force from Short Steered Molecular Dynamics Simulations of Vpu from HIV-1

Vpu from human immunodeficiency virus type-1 (HIV-1) is an 81 amino acid type I integral membrane protein. Vpu forms ion conducting homooligomeric assemblies. To assess the energy landscape of an ion traversing the channel or pore single ion potentials of mean force (PMF) are reconstructed from short (1.2 ns) steered molecular dynamics (SMD) simulations using the Langevin equation of motion. For the simulations a section of the first 32 amino acids including the transmembrane domain of the Vpu protein is used. The values for the friction coefficient are estimated as a function of time using the velocity autocorrelation method. The PMFs of K(+), Na(+), and C(-) adopt a wave like pattern with a maximum around the hydrophobic stretch of the pore and a minimum at the hydrophilic site (C terminus). Independent of the pore size the amplitude of the PMF of at least one cation is always the lowest.