Figure 4.
Stochastic thin filament modeling of TPM1 E192K variant.(A) Stochastic model of thin filament activation incorporating homozygous (HOM) and heterozygous (HET) myofilament composition with simulations of in vitro motility (IVM) and isometric intact twitch. (B) WT IVM data and model fit for determining baseline parameters. (C) Calcium transient from WT EHT. (D) Isometric twitch from WT EHT and model fit for determining baseline parameters in response to the calcium transient. (E) Prediction of p.E192K IVM with decreased stiffness, which does not exhibit decreased calcium sensitivity. (F) Predicted twitches for WT1 and p.E192K. (G) Fitting of p.E192K IVM with decreased stiffness and decreased blocked-to-closed (BC) equilibrium constant. (H) Predicted twitches for WT1 and p.E192K. (I) Normalized predicted twitches for WT1 and p.E192K. arb., arbitrary; Norm., normalized; Vel., velocity.

Stochastic thin filament modeling of TPM1 E192K variant. (A) Stochastic model of thin filament activation incorporating homozygous (HOM) and heterozygous (HET) myofilament composition with simulations of in vitro motility (IVM) and isometric intact twitch. (B) WT IVM data and model fit for determining baseline parameters. (C) Calcium transient from WT EHT. (D) Isometric twitch from WT EHT and model fit for determining baseline parameters in response to the calcium transient. (E) Prediction of p.E192K IVM with decreased stiffness, which does not exhibit decreased calcium sensitivity. (F) Predicted twitches for WT1 and p.E192K. (G) Fitting of p.E192K IVM with decreased stiffness and decreased blocked-to-closed (BC) equilibrium constant. (H) Predicted twitches for WT1 and p.E192K. (I) Normalized predicted twitches for WT1 and p.E192K. arb., arbitrary; Norm., normalized; Vel., velocity.

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