HIV-RT Project
From Harlem
[edit] Ligand Free Structure of HIV-1 Reverse Transcriptase
The ligand free structure (1DLO) is shown below with the top 3 modes obtained from the essential dynamics of the entire 20 nanoseconds of the molecular dynamics simulation. The first and global mode (accounting for over 33% of the overall dynamics of the protein), shows the RNAse H domain to be moving towards the large cleft region. The second mode shows the motion of the p66-fingers towards the p66-thumb regions. The most interesting mode of biological interest is mode 4, which accounts for about 8% of the overall dynamics, which shows the separation of the p66-fingers and p66-thumb regions, which is essential in order to accommodate a large ligand like DNA/ RNA or a response to a small ligand like nevarapine binding to the active site, close to the polymerase active site.
Mode 4 from essential dynamics reveals that the p66-fingers and p66-thumb regions undergo a distinct rotation that causes them to move apart. There is one axis passing along the vertical axis of the p66-thumb region around which this rotation happens in the anti-clockwise direction. The rotation of the p66-fingers also happens across the height-axis but in a clockwise direction. This opposite direction of motion may cause the fingers and thumb regions to separate gradually, or this motion may get enhanced due to ligand binding.
On closer examination of the dynamics, the first 15 nanoseconds of the simulation showed higher correlation between the p66-fingers and thumb region. The last 5 nanoseconds showed high anti-correlation between the p66-fingers and p66-thumb regions. Hence essential dynamics was performed on this part of the trajectory, and the dominant (global) mode of this section of the trajectory showed the separation of the two regions. The ligand free structure (1DLO) is shown below with the top 3 modes obtained from the essential dynamics of the last 5 nanoseconds of the molecular dynamics simulation. The first mode shows the separation of the p66-fingers and p66-thumb regions.
[edit] Double stranded DNA bount HIV-1 Reverse Transcriptase
