Modeling Ions Using Discrete Molecular Dynamics (DMD) (2009)

Undergraduates: Brittany Fotsch, Srinivas Ramachandran

Faculty Advisor: Nikolay Dokholyan
Department: Chemistry

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The overall goal of our project is to develop methodology for and study 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, and for meaningful DMD simulations of ion translocation across channels, it is essential to demonstrate that DMD simulations of ionic diffusion are consistent with well-characterized molecular dynamics (MD) simulations and experimental observations. In the current study, we determine the diffusion coefficients of both monovalent and divalent cations using DMD computation engine developed in our lab. We perform numerous MD and DMD simulations of different concentrations of KCl and CaCl2. We test the validity of our approach by demonstrating that DMD simulations are able to quantitatively reproduce diffusion coefficients of K+ and Ca2+ ions obtained experimentally and from MD simulations that use explicit solvent. The radial distribution functions are also calculated for all ion combinations in each simulation. Computational characterization of ionic currents across channels is a great challenge and the validation of ions in DMD will now allow us to use DMD to quantitatively characterize ionic currents across channels such as ryanodine receptor 1 (RyR1) to gain further insight into their functional mechanisms.