Fig 1.
Cartoon schematic of HIV-1 mRNA export complex and nuclear pore complex.
Fig 2.
Flowchart of the hybrid computational protocol used for protein-protein binding mode prediction.
Fig 3.
Superposition of the top 10 (for each host structure) ClusPro2.0 docked structures.
The structures are shown for (A) 3NBZ (w/RanGTP) back side (B) 3NBZ front side, and (C) 3GB8 (w/o RanGTP) back side, and (D) 3GB8 front side. CRM1 is shown in silver and RanGTP is the yellow ribbon structure. The arrow points to the Rev-NES peptide.
Table 1.
Calculated structural and energetic quantities for the 60 docked structures with rankings.
Fig 4.
Residues with ΔGmut→Ala >1 kcal/mol highlighted on the molecules from DDX3-CRM1-RanGTP complex.
(A) CRM1 back, (B) CRM1 front, (C) and (D) DDX3. Color scale from white (~1 kcal/mol) to red (>2 kcal/mol). Blue indicates 0 kcal/mol. The arrow points to the Rev-NES peptide.
Fig 5.
Residues with ΔGmut→Ala >1 kcal/mol highlighted on the molecules from DDX3-CRM1 complex.
(A) CRM1 back, (B) CRM1 front, (C) and (D) DDX3. Color scale from white (~1 kcal/mol) to red (>2 kcal/mol). Blue indicates 0 kcal/mol. The arrow points to the Rev-NES peptide.
Fig 6.
DDX3 molecules from top 6 docked structures overlapped together.
Table 2.
List of interfacial warm and hot residues (ΔGmut→Ala > 1kcal/mol) for top 6 docked structures obtained from computational alanine scanning.
Table 3.
Calculated structural and energetic quantities for the top 6 docked structures with rankings after extended MD simulation.
Fig 7.
Calculated structural and energetic quantities for extended MD simulation.
(A) CRM1-NES-RanGTP—DDX3 interaction energy, (B) RanGTP—DDX3 energy, (C) RMSD, and (D) BSA are plotted over the course of the 50 ns extended MD simulations.
Table 4.
Summary of salt bridge pairs formed throughout extend MD simulation.
Fig 8.
Snapshot of residues at the interface and salt bridge pairs for (3NBZ) ClusPro#7.
CRM1 is shown in silver and DDX3 and RanGTP are the orange and yellow ribbon structures, respectively. The green thread is Rev NES. Acidic and basic residues involved in salt bridges are shown in red and blue transparent surfaces, respectively. Top inset shows a zoomed in view of salt bridges around the center of CRM1. Right inset shows zoomed and rotated aerial view of salt bridges near NES region of CRM1. See Table 4 for specific salt-bridge pairs.