Structural dynamics of V3 loop with different electrostatics: implications on co-receptor recognition: a molecular dynamics study of HIV gp120.

The HIV's envelope glycoprotein gp120 plays a major role in the entry of the virus into the host cell, through its successive interactions with the cell surface CD4 receptor and a co-receptor (CCR5 or CXCR4). The choice of a specific co-receptor by gp120 has an important consequence on HIV infection and pathogenesis. The third variable region within gp120, the V3 loop, is the principal determinant of the co-receptor usage by gp120. Here, we report the long time molecular dynamics simulations of four gp120 structures, having a V3 loop charge of +3 and +5, from both R5 and X4 specific strains of HIV. The results of the study highlight the properties of the V3 loop that can be critical for dictating the co-receptor recognition and selection in structural context. In detail, we observe that the structural orientation of the V3 loop in the 3D space is modulated by its net charge, whilst its co-receptor choice is likely dictated by a combined effect of both the electrostatics of the loop and its conformational variability at the level of its central crown region.