Modeling Ionic Translocation Across Ryanodine Receptor 1 Using Discrete Molecular Dynamics (DMD) (2010)

Undergraduates: Brittany Fotsch, Srinivas Ramachandran

Faculty Advisor: Nikolay Dokholyan
Department: Chemistry

---

The overall goal of our project is to develop methodology for studying ion translocation across biological channels, especially Ryanodine receptors using discrete molecular dynamics (DMD). Ion translocation occurs at time scales that are not achievable by traditional atomistic simulations. However, DMD's novel algorithm enables us to study long time-scale processes, such as ion translocation across channels. We first demonstrate that DMD simulations of ionic diffusion are consistent with well-characterized molecular dynamics (MD) simulations and experimental observations by comparing diffusion coefficients of both monovalent and divalent cations and radial distribution functions for all ion combinations. We then use DMD to quantitatively characterize ionic currents across ryanodine receptor 1 (RyR1) to gain further insight into its functional mechanism. We build a model of RyR1 using the interior radius of the channel. Both Coulomb’s Law and Lennard-Jones Potential are used to govern the interactions between ions in the simulation, and various potential differences are applied across the channel. Models containing only potassium ions and both potassium and calcium ions are created. We validate our model by comparing current measurements for various potential differences applied across the channel with experimental observations. Our results agree with experimental results within error and reproduce the effect of the addition of calcium ions to RyR1.