The Spark of Life: Understanding Nature’s Ion Channel Design via Computation (Co-hosted with Chemistry)

The structure and function of Nature’s voltage gated cation channels (VGCC) has been largely understood through decades of elegant experimental work based on electrophysiology, pharmacology, and crystallography. More recently, computer simulation, especially molecular dynamics (MD) calculations have contributed atomic level information to be compared with experimental data, thereby allowing validation of the models and protocols. Importantly, MD can shed light on elements of VGCC function that cannot be readily obtained from “classical” experiments. I will first review the history of the field. Then, I will focus on recent contributions from MD on the structure and function of VGCCs. with emphasis on the voltage sensor domain (VSD), highlighting: the motion of key structural motifs during channel activation; the nature of the intermediate states when the channel transitions from open to closed; and the role of amino acid mutations in certain genetic diseases.

Michael Lawrence Klein is Laura H. Carnell Professor of Science and Director of the Institute for Computational Molecular Science in the College of Science and Technology at Temple University in Philadelphia, USA. He was previously the Hepburn Professor of Physical Science in the Center for Molecular Modeling at the University of Pennsylvania.

Klein obtained a B.Sc. from the University of Bristol in 1961, followed by a Ph.D. in 1964. He was a researcher at the National Research Council 1968-1987, and joined the faculty of the University of Pennsylvania in 1987. 

Klein's research in computational chemistry, particularly statistical mechanics, intermolecular interactions, and modelling of condensed phases and biophysical systems, is among the most highly cited in the field. He received the Aneesur Rahman prize in 1999, which is the highest honor given by the American Physical Society for work in computational physics, and was elected to the United States National Academy of Sciences in 2009.