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Workshops

Ion Transport from Physics to Physiology: the Missing Rungs in the Ladder

April 3, 2017 to April 5, 2017
Location : CECAM-HQ-EPFL, Lausanne, Switzerland
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Markov State Model approaches to molecular kinetics: toward modeling ion transport mechanisms

Vincent Voelz
Temple University, Philadelphia, USA, USA

Abstract

In recent years Markov State Model (MSM) approaches to conformational dynamics have been used with great success to model protein folding kinetics and pathways. In these methods, molecular simulations are used to sample transitions between metastable conformational states, to construct a kinetic network model that can predict long-timescale dynamics from ensembles of much shorter non-equilibrium trajectories. Because MSMs approaches offer a way to explicitly model microscopic kinetics, they should have key advantages in modeling ion transport mechanisms. Molecular simulation work has often relied on thermodynamic profiling as a proxy to estimate kinetic barriers, potentially obscuring kinetic mechanisms. MSM methods also offer a way of connecting more directly with physiological experiments, which are often non-equilibrium in nature. In my talk, I discuss some of our recent work using MSMs to model conformational dynamics, and new MSM-based approaches that our group and others have developed to efficiently predict how kinetics are affected by mutations and other perturbations, and how to construct kinetic models from thermodynamically-biased simulations. Hopefully this will provoke further discussion about what challenges need to be overcome in applying these methods to the vital problem of modeling ion transport.