X-ray Diffraction Simulations

From molecular simulations to experimentally interpretable diffraction patterns

From simulated molecular structure to diffraction readouts

X-ray fiber diffraction is a key method for studying muscle structure during contraction, but interpreting diffraction patterns requires a mechanistic model. FilamenTech developed forward-modeling methods using MUSICO to predict diffraction patterns directly from simulated molecular configurations.

Key findings:

Predicted diffraction patterns from simulated actin-myosin structures.

Connected molecular configurations, force generation, and experimental diffraction readouts.

Demonstrated how nonuniform strain changes diffraction behavior in helical molecules.

Established a forward-simulation path for integrating MUSICO with X-ray experiments.

This case study shows how FilamenTech links molecular muscle structure to measurable diffraction data, creating a structural validation layer for mechanistic simulations.

References:
Prodanovic et al., J Appl Cryst. 2016
Prodanovic et al., Int J Mol Sci. 2023
Prodanovic et al., Int J Mol Sci. 2025

$(Top) All-atom and coarse-grained representations of an actin filament with MUSICO-predicted nonuniform axial strain distribution in the contracted state, where local monomer spacing varies continuously along the filament reflecting heterogeneous forces from stochastic crossbridge binding. (Bottom) MUSICO-X predicted X-ray fiber diffraction patterns from contracted actin filaments comparing the all-atom model (left column) and coarse-grained model (right column), showing the first three meridional reflections at 27.3 Å, 13.6 Å, and 9.1 Å. Agreement between the two model resolutions validates the coarse-grained approach for efficient large-scale diffraction prediction from MUSICO simulations.$

MUSICO-predicted actin monomer spacing along contracted filament length for five independent experiments (2a, 2d, 8a, 8c, 11c), showing the characteristic stochastic step-increase in spacing driven by randomly distributed bound crossbridges. The variability between filaments reflects the heterogeneity of local force distribution in living contracting muscle.

$(Top) Relationship between actin spacing change and inverse actin monomer spacing in contracted muscle, derived from MUSICO simulations fitted to experimental X-ray meridional reflections. (Bottom) Frequency histograms of thin filament forces (pN) extracted from MUSICO for four experiments, demonstrating the distribution and variability of forces in living muscle. This approach enables quantification of local actin filament forces from X-ray diffraction data, a measurement inaccessible by any other experimental or analytical technique.$

Human cardiac prediction from data you already have.

FilamenTech develops multiscale mechanistic simulation workflows that help drug-development teams translate assay, tissue, animal, mutation, and structural data into human-relevant cardiac and muscle predictions.

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Evaluate mutation effects, drug responses, or translational hypotheses using mechanistic simulation workflows tailored to your program.

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