Allosteric modulation of cardiac myosin dynamics by omecamtiv mecarbil
Fig 8
Preferential connections in the local correlation network between the OM-binding site and functional regions in cMotorD.
A. Plot of the difference between OM and Apo preferential connection scores (Δζ), calculated using fragment V698 as source site. The scores are derived from a consensus correlation matrix calculated over the four simulations of each binding state. A negative value indicates a stronger preferential connection to V698 in OM-bound simulations compared to Apo ones. Negative bars are coloured according to the subdomain. The position of DCM-related mutations is indicated with a yellow dot. Grey areas highlight the position of functional regions, namely the seven strands of the central β-sheet (b1 to b7), the P-loop (P), the F helix (FH), Loop 1 (L1), the G helix (GH), Switch 1 (SW1), the β-bulge (bb), the OH loop (OH), Switch 2 (SW2), the Strut (St) and the SH1 helix (SH1). The inset shows a close-up view of the fragments in the F-helix, the loop L1 and the G-helix (resid 185–228). B. Mapping of the Δζ scores onto the initial structures of OMA1. Only regions with negative values are coloured. The thickness of the tube is proportional to the magnitude of Δζ values. A close-up view of the F-helix, the loop L1 and the G-helix is shown in the inset, with the position of residues I201 and A223 indicated by yellow spheres.