Abstract
The structure and ion channel activity of the viral ion channels Vpu from human immunodeficiency virus type I (HIV-1) and 3a from SARS Coronavirus (SARS-CoV) have not been characterised in atomistic detail, in spite of the physiological importance of these ion channels. We have modelled several possible oligomeric states for Vpu, and carried out extensive molecular dynamics (MD) simulations in a lipid bilayer environment. Our results show that the pentamer is the most stable oligomeric form, with van der Waals interactions being the dominant force in holding together the monomeric units. The mechanism of ion conduction through the pentameric form has been investigated by umbrella sampling free energy calculations. We suggest that only one ion can pass through the channel at a time, rather than a continuous stream of ions; this is in agreement with experimental conductance studies [1]. We have also modelled possible structures for a monomeric unit of the ion channel SARS 3a, which has three helical transmembrane (TM) domains connected by loops [2]. Based on residue orientation, clusters of hydrophilic residues have been identified in each TM domain, and, by considering all possible orientations of these hydrophilic clusters, a number of monomers have been modelled and equilibrated in a membrane environment. We shall be presenting model structures of both monomeric and oligomeric states of 3a