PCA plot comparing conformational dynamics sampling between the apo, Ca^{2+}-bound and Ca^{2+}-TnI-bound system. The principal component space generated by known structures of TnC is shown along with molecular dynamics trajectories that are projected into the first versus second principal component space of known TnC structures. (A) Projections of known pdb structures are shown as filled circles. The NMR structures of 1AP4, 1SPY, and 1MXL are shown as filled green, red, and blue circles, respectively. (B) Projections of the Ca^{2+}-bound TnC for the 1AP4 cMD trajectory (full blue circles), the 1SPY cMD trajectory (full red circles), and the 1MXL cMD trajectory (full green circles) into the PC space are shown in density coloring, where darker shades of blue, red, and green indicate the more heavily sampled parts of the trajectories. (C) Projections of the Ca^{2+}-bound TnC for the 1AP4 aMD trajectory (full blue circles), the 1SPY aMD trajectory (full red circles), and the 1MXL aMD trajectory (full green circles) into the PC space are shown in density coloring, where darker shades of blue, red, and green indicate the more heavily sampled parts of the trajectories. For the conventional molecular dynamics simulations, the principal component space sampled by the apo and Ca^{2+}-bound systems is almost identical indicating similar dynamics. In the aMD simulations, however, occasional excursions of the Ca^{2+}-bound system into Ca^{2+}-TnI-bound-like states are observed. The Ca^{2+}-TnI-bound system, however, samples a different, hardly overlapping region of the PC space, suggesting a change in dynamics upon TnI binding.

## PubMed Commons