Fig 2. Cooperative binding of small molecules to the central hexamer cavity.

Two-dimensional free energy landscapes of dATP translocation through the cavity, in the presence of (a) an additional dATP, (c) IP₆, or BHC (e). The horizontal reaction coordinates (in Å) represent the location of the COM of a dATP molecule on the cavity axis, which connects the exterior and interior of the capsid (respectively right and left). The vertical reaction coordinates (in Å) are the positions of the COM of (a) a second dATP, (c) IP₆, or (e) BHC on the progress variable along the central hexamer axis. The magnitudes of the free energies are indicated in the color scalebar in units of kcal/mol. Pathways connecting the interior and exterior are shown as a dashed line, and representative structures corresponding to these translocation events are illustrated in (b), (d), and (f). Numerical data for panels A, C, and E can be found in S2 Data. BHC, benzenehexacarboxylic acid; COM, center of mass; dATP, deoxyadenosine triphosphate; IP₆, inositol hexakisphosphate.