(Saturday, 4/4/2020) [Mountain Time (GMT-6)]
Purpose: To determine the suitability of the EYKY (Glutamic Acid-Tyrosine-Lysine-Tyrosine) peptide as an imaging probe via preliminary investigation of EYKY’s self-assembly behavior and of the stability of the resulting conformations.
Methods: Molecular dynamics (MD) simulations were used to simulate 100 EYKY molecules in an aqueous solution at a temperature of 303 Kelvin and a pressure of 1 bar. Using a coarse-grained force field, the peptides and water molecules were mapped into simpler representations. The simulation was performed for 5 microseconds, proceeding with a time step of 25 femtoseconds. Analysis was then performed to analyze the resulting conformations and their stabilities. The radius of gyration (Rg), solvent-accessible surface area (SASA), and free energy landscape (FEL) are used to measure the stability of the conformations.
Results: The EYKY system aggregates quickly, reducing its SASA more than four-fold in the first 500 nanoseconds of simulation. In the remaining time, the SASA value stabilizes, apparently indicating a stable conformation. The system’s Rg value, however, does not stabilize during the simulation, thus suggesting a lack of stability of the conformation. The system’s FEL confirms these findings, indicating low free energy values at low SASA values but with essentially no dependence on Rg.
Conclusion: This work indicates that more investigation is needed to determine the stability of EYKY’s conformations and therefore to determine its suitability for applications as an imaging probe. The constancy of the EYKY system’s SASA juxtaposed with the large variance in its Rg yield an ambiguous conclusion about the stability of its conformation. Given that outcomes in MD simulations are ultimately stochastic, these results alone do not undermine EYKY’s potential as an imaging probe; they instead expose a preliminary approach to modeling EYKY and highlight the need for more simulations to be performed.
Funding Support, Disclosures, and Conflict of Interest: J Miles was funded by the AAPM Education and Research Fund. The authors declare no disclosures nor conflicts of interest.
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