A spatially detailed myofilament model as a basis for large-scale biological simulations

The availability of increased computing power will make possible new classes of biological models that include detailed representations of proteins and protein complexes with spatial interactions. We develop such a model of the interaction of actin and myosin within one pair of thick and thin filaments in the cardiac sarcomere. The model includes explicit representations of actin, myosin, and regulatory proteins. Although this is not an atomic-scale model, as would be the case for molecular dynamics simulations, the model seeks to represent spatial interactions between protein complexes that are thought to produce characteristic cardiac muscle responses at larger scales. While the model simulates the microscopic scale, when model results are extrapolated to larger structures, the model recapitulates complex, nonlinear behavior such as the steep calcium sensitivity of developed force in muscle structures. By bridging spatial scales, the model provides a plausible and quantitative explanation for several unexplained phenomena observed at the tissue level in cardiac muscles. Model execution entails Monte-Carlo-based simulations of Markov representations of calcium regulation and actin-myosin interactions. While most of the results presented here are preliminary, we suggest that this model will be suitable to serve as a basis for larger-scale simulations of multiple fibers assembled into larger sarcomere structures. © 2006 IBM.