Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5371342 | Biophysical Chemistry | 2011 | 12 Pages |
T-20 (also known as enfuvirtide) is a fusion inhibitor peptide known to have some effectiveness in the control of progression of HIV infection by inhibiting the fusion of the HIV envelope with the target cell membrane. Recent results indicate that T-20 is able to interact with membranes in the liquid disordered state but not with membranes in an ordered state, which could be linked to its effectiveness. A detailed molecular picture of the interaction of these molecules with membranes is still lacking. To this effect, extensive molecular dynamics simulations (100Â ns) were carried out to investigate the interaction between T-20 and bilayers of 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) and POPC/cholesterol (1:1). Membrane properties such as area/lipid, density profiles, order parameters and membrane thickness were studied. It was observed that T-20 has the ability to interact to different extents with both model membranes in this study and that peptide interaction with the bilayer surface has a local effect on membrane structure. The formation of hydrogen bonding between certain peptide residues and the POPC phosphate group was observed. However, T-20 showed a more limited extent of interaction with model membranes when compared with other, more efficient, peptides (such as T-1249). This effect is most notable in POPC/Chol membranes in which interaction is especially weak, owing to less peptide residues acting as H bond donors to POPC and virtually no H bonds being formed between T-20 and cholesterol. This lower ability to interact with membranes is probably correlated with its smaller inhibitory efficiency.
Graphical abstractDownload full-size imageHighlights⺠HIV fusion inhibitor T-20 (enfuvirtide) was studied by molecular dynamics simulations. ⺠The inhibitor peptide was simulated in both POPC and POPC/Cholesterol 1:1 bilayers. ⺠T-20 showed a more limited extent of interaction with model membranes than T-1249. ⺠Interaction with POPC/Cholesterol bilayers is especially weak, no penetration occurs. ⺠The weaker interaction with membranes correlates with a smaller inhibitory efficiency.