Viral Protein U (Vpu) is an accessory protein of the HIV-1 virus and a member of the Viral Channel Forming protein (VCP) family. A HIV-1 virus with Vpu is 10 times more infectious than a Vpu deficient HIV-1 virus.

Vpu consists of 81 amino acids, with one transmembrane (TM) helix close to the N-terminus and two cytoplasmic (Cyto) helices. It is involved in more than ten different activities. The most well studied functions are CD4 degradation and BST2 antagonism. Vpu also forms an ion channel. However, its functions, structure, and mechanisms currently remain unclear.

This research focuses on looking for a better insight into Vpu-mediated channel activity. Computational simulations using Molecular Dynamics (MD) have provided a way to overcome the experimental limitations. AMBER is a MD package to simulate biological systems at an atomistic level of detail. Its lipid force-field, Lipid 14 (recently updated to lipid 17, unpublished) contains a range of parameters for lipid head and tail groups separately, enabling a variety of lipids to be simulated by mix-and-match different head and tail combinations. Nowadays, much longer and more accurate computational simulations can be achieved.

This project has first evaluated the lipid force-field, and developed a systematic methodology to perform all-atom membrane-protein simulations. The key biological finding is that a single full-length Vpu monomer can support a pore, as opposed to the necessity for a Vpu oligomer, as has previously been suggested. The results indicate that a variety of Vpu oligomers co-exist, resulting in a range of pores with various sizes. The pores observed at higher oligomeric states are closer to a ring-like structure. The transportation of substances (K+, Cl- and POPS) across the membrane is facilitated by the Vpu-mediated pore. A cationic selectivity is observed in the spontaneous ion translocation, which is confirmed using potential-of-mean-force (PMF) simulations.