1. Curling of Flap Tips in HIV-1 Protease as a Mechanism for Substrate Entry and Tolerance of Drug Resistance 
Walter R.P Scott, Celia A Schiffer 
Structure 
Volume 8, Issue 12, Pages (December 2000)
DOI: /S (00)

2. Figure 1
Snapshots of the Backbone Conformation of HIV-1 Protease throughout the Trajectory at 1 ns Intervals of the Unliganded Structure and Substrate Bound Complex
(a) The unliganded structure.
(b) The substrate bound complex.
The catalytic Asp-25 is highlighted in green. In the unliganded structure the glycine-rich flap tips, highlighted in black, curl into a hydrophobic cluster. The figure was generated with UCSF MidasPlus [30]
Structure 2000 8, DOI: ( /S (00) )

3. Figure 2
Root-Mean-Square Deviations of the α-Carbon Backbone Positions for the Unliganded and Liganded Protease Simulations
Rmsd for the unliganded (red) and liganded (black) protease simulations are calculated over 10 and 5 ns, respectively. The two plots show the two monomers in HIV-1 protease
Structure 2000 8, DOI: ( /S (00) )

4. Figure 3
Stereodiagrams of the Tip of the Flap in the Crystal Structure and in the Structures at 3 and 10 ns
The tips of the flaps are shown in magenta. Cyan highlights the packing of Ile-50 against the P1-loop, residues 79–81, and Val-32.
(a) Crystal structure [4, 15].
(b, c) The simulated flap conformations of each monomer after 3 ns.
(d) The same monomer as shown in (c) at 10 ns. In the crystal structure, the extended flap conformation blocks access to the active site. The curling movement of the tips of the flap exposes the active site to solvent and simultaneously buries many hydrophobic residues in a cluster at. The flap of each monomer adopts a slightly different conformation in the simulation, and these conformations vary with time. UCSF MidasPlus [30] was used to generate the figure
Structure 2000 8, DOI: ( /S (00) )

5. Figure 4 Isoelectric Contour and Molecular Surface
(a) The unliganded dimer structure from the crystal structure of 1hhp [4,15].
(b) The conformation of the dimer after 3 ns of molecular dynamics, when the tips of the flaps are curled.
The top view shows isoelectric surface contours calculated at +3 kT in blue and −3 kT in red. The bottom panel shows the molecular surfaces from a view looking down at the flaps from above the dimer axis. The curling of the flaps dramatically changes the electrostatic potential that the substrate would encounter upon binding. Access to the electronegative active site is gained when the flaps curl in. Four of the octomeric substrates have a net positive charge, and another four are neutral. Therefore, the hydrophobic walls and negative base of the active site should guide potential substrates into an optimal conformation for cleavage. Figures were generated with GRASP [31]
Structure 2000 8, DOI: ( /S (00) )

6. Figure 5
Ramachandran Plots of Residues Gly-48, Ile-50, and Gly-51 in Both Monomers
Each point on the plot represents a conformation sampled over 5 ns of simulated time. Figures made with a modified version of the program PROCHECK [32]
Structure 2000 8, DOI: ( /S (00) )

7. Figure 6
Snapshots of the Backbone Conformation of HIV-1 Protease and the Protease Variant where Gly-51 Has Been Substituted with an Asparagine after 1 ns of Vacuum
The HIV-1 protease is shown in magenta, and the protease variant where Gly-51 has been substituted with an asparagine is shown in cyan. The figure was generated with UCSF MidasPlus [30]
Structure 2000 8, DOI: ( /S (00) )