Major subdomain rearrangement in HIV-1 reverse transcriptase simulated by molecular dynamics.

We have performed eight 1-ns in vacuo molecular dynamics simulations of HIV-1 reverse transcriptase (RT). Starting with the p66 thumb subdomain in an upright configuration, the p66 thumb moved down over the palm during six of the eight trajectories, in excellent agreement with the crystallographic structure of unliganded RT. The large rearrangement of the p66 thumb subdomain, its tip moving approximately 30 A, occurs during the first 30-200 ps. This approach may allow a detailed study of the processes involved in biologically significant conformational changes in macromolecules.