The structure of a short fragment of the human HIV-1 membrane glycoprotein gp41 has been examined using a combination of parallel tempering molecular dynamics (PTMD) and far UV circular dichroism spectroscopy. The aim is to resolve conflicting reports on the solution state conformational bias in this membrane proximal domain spanning the epitope for the 2F5 monoclonal antibody. We conclude that gp41(659-671) exhibits conformational plasticity in which competing folding propensities are present and can be influenced by local microenvironment. Contrary to previous reports, the 3(10) helix does not emerge as a dominant motif from either simulation or experiment, and this peptide is therefore not a model system for this fold type. Other fold groups such as turn motifs are identifiable at elevated temperatures in the PTMD trajectories and are potentially relevant in antibody binding. Helical populations in pure water are significantly overestimated according to the CHARMM parametrization. However, circular dichroism (CD) data show that helices are promoted in membrane mimetic solvents. As this is a membrane proximal peptide, the helical motif may well have physiological significance.