Peter Jordan
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| Professor of Chemistry Ph.D., Yale University, 1960781-736-2540 jordan@brandeis.edu |
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Understanding the physicochemical bases for controlled transport of ions and water across biomembranes is a major research area in biophysics. Transmembrane permeation of charged and polar species is mediated by specialized proteins, which form water filled channels. Recent advances in X-ray structure determination provide the needed scaffolding for the use of modern theoretical methods and the impetus for developing new techniques, all designed to understand the behavior of these highly specialized molecules. We focus on channel forming proteins and their phospholipid environment, with three major goals: (1) developing new methods for clarifying channels' selectivity mechanisms; (2) developing techniques for determining reaction pathways between their various conformational states; (3) determining how phospholipid-protein interaction influences these conformational equilibria.
Channel Selectivity. Transmembrane permeation of small species is mediated by channel proteins. In their absence the energy barriers for transport would be prohibitive. Aqueous pores, in addition to make transport possible, are highly discriminating. Some select for K^+ , other for Na^+ ; some allow only anion passage; yet others permit water passage but reject all ions. Sometimes protein structure provides clear indication of the permeation pathways but only hints as to the discrimination mechanism. In others cases the pathway is tortuous, and not structurally self-evident. As part of our goal of relating structure and function in physiologically significant molecules we are developing methods for establishing permeation pathways (reaction coordinates) and the associated energetics in this latter case.
Channel Gating. Channels control transmembrane flux by gating, conformational rearrangement between one (or more) "open" states and a number of "closed" ones. These important processes are much too slow to be studied by molecular dynamics simulation. In order to establish the underlying mechanisms, we are developing ways to identify cooperative, low frequency, high amplitude structural modes that are associated with such transitions.
Membrane-Channel Interaction. Protein channels, such as those associated with auditory sensation, respond to mechanical stress, and should thus be particularly influenced by their membrane environment. As channels are often formed by subunit association, transitions among their various closed and open states are sensitive to interaction with their surroundings. We are developing simple methods for describing such processes.
Selected References
(Click here for a complete list of publications)
"Semi-Microscopic Modeling of Permeation Energetics," IEEE Transactions on Nanobioscience, 2005, 4:94-101
"Fifty Years of Progress in Ion Channel Research," IEEE Transactions on Nanobioscience, 2005, 4:3-9
"Permeation in ion channels. The interplay of structure and theory," Trends in Neurosciences, 2004, 27:308-314; with G. V. Miloshevsky
"Modeling permeation energetics in the KcsA potassium channel" Biophys. J., 2003, 84[5]:0000; with S. Garofoli
"Ion-water interaction potentials in the semi-microscopic model" J. Chem. Phys., 2003, 118:1333-1340; with V. L. Dorman
“Energetics and gating of narrow ionic channels: The influence of channel architecture and lipid-channel interactions,” in Interfacial Catalysis, A.G. Volkov, ed.; Marcel Dekker, 2003, 493-534; with G. Miloshevsky and M.B. Partenskii
“Permeation energetics in a model potassium channel,” in Ion channels-from atomic resolution to functional genomics; Novartis Found Symp 245, Wiley, Chichester, 2002, 109-121; with S. Garofoli, G. Miloshevsky and V.L. Dorman
"Ionic energetics in narrow channels," in Proceedings of the IMA Workshop on Membrane Transport and Renal Physiology, H. E. Layton & A. M. Weinstein, ed.; Springer-Verlag, 2002, 1-25
"Trial by ordeal: Ionic free energies in gramicidin" Biophys. J., 2002, 83: 1235-1236.
"Unclogging a pipe: Potassium channel pinball" Biophys. J., 2002, 83: 2-4.
"Membrane deformation and the elastic energy of insertion: Perturbation of membrane elastic constants due to peptide insertion" J. Chem. Phys. , 2002, 117:10768-10776; with M. B. Partenskii
“Electroelastic instabilities in double layers and membranes,” in Liquid Interfaces in Chemical, Biological, and Pharmaceutical Applications, A.G. Volkov, ed.; Marcel Dekker, 2000, 51-82; with M.B. Partenskii
"Membrane capacitance: A non-local electroelastic treatment," Mol. Phys., 2000, 98:193-200; with M.B. Partenskii.
"Ionic interactions in multiply occupied channels, " in Gramicidin and related ion-channel forming peptides; Novartis Found Symp 225, Wiley, Chichester, 1999, 153-169; with V.L. Dorman and S. Garofoli
"Ion permeation and chemical kinetics," J. Gen. Physiol., 1999, 114:601-603.
"Membrane stability under electrical stress. A non-local electroelastic treatment," J. Chem. Phys., 1998, 109, 10361-10371; with M.B. Partenskii and V.L. Dorman.
“Comparison of Selectively Polarizable Force Fields for Ion-Water-Peptide Interactions: Ion Translocation in a Gramicidinlike Channel,” J. Phys. Chem. B, 1998, 102, 9127-9138; with K.A. Duca.
"Ion-water and water-water interactions in a gramicidinlike channel: Effects due to group polarizability and backbone flexibility," Biophys. Chem., 1997, 65, 123-141; with K.A. Duca.
"A semi-microscopic Monte Carlo study of permeation energetics in a gramicidinlike channel. The origin of cation selectivity," Biophys. J. 1996, 70, 121-134; with V. Dorman and M.B. Partenskii.