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Center for Nonlinear Studies |
Heart failures and aberrant heart rhythm (arrhythmias) due to the dysfunctions of ion-selective channels cause more deaths than cancers in North America. I will present the latest understanding of ion selectivity mechanisms in potassium-selective and sodium selective channels. I will discuss how the computational studies on the ion selectivity and affinity expose many problems in current simulation force fields and simulation techniques. In an effort to improve the accuracy of force fields, I will show some benchmarking results on Drude force fields in Gramicidin A channel and bacterial voltage-gated sodium-selective channel (NavAb). I will also discuss our current development for a non-equilibrium sampling technique to re-construct two-dimensional free-energy landscapes, particularly for understanding multiple-ion permeation pathways in potassium-selective channel, namely KcsA. Finally, I will demonstrate a typical case where we now can systematically study in silico the binding of drugs in ryanodine receptors, which are also critical to the studies of arrhythmias and heart failures.
Host: Angel Garcia