I³MS - Dreyer Seminar
Dr. Jens Dreyer - Large-Scale ab initio Applications in Biophysics
Computational Biophysics, German Research School for Simulation Sciences
Biological ion channels are pore-forming transmembrane proteins which selectively regulate transport of ions in and out of every living cell. Dysfunction of ion channels are at the basis of several diseases called channelopathies, including, for instance, cystic fibrosis, epileptic seizure, diabetes and migraine .
The mechanism of proton transport in ion channels is investigated entirely by first principles molecular dynamics simulations applying Car-Parrinello methods . We focus on the monovalent ion selective channel Gramicidin A . The transport of excess protons along the 1-dimensional wire of water molecules inside the Gramicidin channel is faster (a single conduction event takes about 500 ps) than in any other narrow-pore biological channel conducting H+ or other monovalent ions . We calculate free energy profiles using metadynamics  and analyze the subsequent steps of proton transfer, which involves a detailed understanding of the sequence of alternating hydrogen and chemical bond breaking and making processes, the interplay of the electrostatic interactions imposed by the protein, the membrane and the surrounding water molecules. This project of simulating a fundamental biological system in laboratory-feasible conditions fully from first-principles is made possible by access to supercomputing facilities and support through the PRACE (Partnership for Advanced Computing in Europe) 1st regular call.
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