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Michael E Green

Michael E Green


Physical Chemistry

MR 1130
New York , NY 10031
Office Phone: (212) 650-8373


Physical Chemistry


This is a computational chemistry group, concerned primarily with the gating of voltage-gated ion channels, membrane proteins found in practically every cell; the "gating" of these channels is responsible, among other things, for the nerve impulse. Gating means that the proteins change in some way that allows Na+, or K+ (and in some instances, though not those we work on, Ca2+) to pass through the protein, and thus through the membrane. We have proposed a three step model of the gating process: (1) proton tunneling between two amines starts (2) a proton cascade across the electric field that traverses the membrane, leading to (3) a conformational change (at the intracellular side, in K+ channels) that opens the channel. The proton motion (2) alters the charge on the intracellular side of the channel, causing groups that had been held together by salt bridges and hydrogen bonds to separate (3), because of electrostatic repulsion. Step (2) also produces a capacitative current, called thegating current, that is of the correct magnitude. This model differs sharply from others that have been proposed, in which the possible role of proton transport is not considered, but much larger conformational changes are predicted, including motion of positively charged amino acids to produce the gating current. More recently we have added computations on the cavity of the channel, showing how a K+ traverses the cavity, entering the selectivity filter of the channel against an entropic barrier.

The importance of hydrogen bonds and proton transport in this model has led us to investigate cooperative effects in hydrogen bonding in small clusters, as the potentials that are generally used in simulations ignore these effects, but they are important in small clusters, such as those found in clefts in proteins, like those in ion channels. We are extending these studies in the direction of allowing us to develop a potential that could be used in especially accurate simulations of water in protein clefts and similar confined spaces. We have also done calculations on salt bridges with water added, showing how rings of oxygens form anchored on the salt bridge.

The principal tool we use in our work is ab initio calculation, generally as Density Functional Theory (DFT) calculations. We plan to extend this to work with techniques more appropriate to larger systems, especially simulations, as we develop the new potential for water clusters.

Representative Publications, by topic

I. The three step model:

1. Lu, J., Yin, J. and Green, M. E. (1999) A Model for Voltage Gating with Static S4 Segments, Ferroelectrics 220,249-271

2. Green, M. E. (2002) Water as a Structural Element of an Ion Channel:Gating in the KcsA Channel, and Implications for Voltage-Gated Ion Channels, J. Biomolec. Struct. Dynamics 19,725-730

3. Sapronova, V.S., Bystrov, V.B., and Green, M. E. Water, (2003) Proton Transfer, and Hydrogen Bonding in Ion Channel Gating, Frontiers in Bioscience 8, s1356-1370

II. Proton Tunneling:

1. Yin, J. and Green, M. E. (1998) Intermolecular Proton Transfer between Two Methylamine Molecules with an External Electric Field in the Gas Phase, J. Phys. Chem. A 102, 7181-7190

III. Proton Transport: (see also I, paper 3)

1. Sapronova, V.S., Bystrov, V.B., and Green, M. E. (2003) Ion Channel Gating and Proton Transport, J. Mol. Struct(THEOCHEM) 630,297-307

2. Sapronova, V.S., Bystrov, V.B., and Green, M. E. (2004) Further Calculations on Proton Transfer Relevant to the S4 Transmembrane Segment of Ion Channels, Including Deuterium Motion, Biophys. Soc. Abstracts, Abs. No. 2268

IV. The Importance of Phosphate in Gating:

1. Green, M. E. (2005) A Possible Role for Phosphate in Complexing the Arginines of S4 in Voltage Gated Channels, J. Theor. Biol. 233,337-341

2. Pradhan, P., Ghose, R. and Green, M. E. (2005) Voltage Gating and Anions, Especially Phosphate: A Model System, Biochim. Biophys. Acta (Biomembranes) 1717, 97-103

V. Hydrogen Bonding:

1. Green, M. E. (2002) Partially Charged H5O2+ as a Chemical Switch: A Bond Order and Atoms in Molecules Study of Hydrogen Bonding Determined by Surrounding Groups, J. Phys. Chem. A, 106,11221-11226

2. Kariev, A. M., Znamenskiy, V. S., and Green, M. E. (2007) Quantum Mechanical Calculations of Charge Effects on Gating the KcsA Channel Biochim. Biophys. Acta (Biopmemb)1768, 1219-1229

VI. Cooperative Effects in Hydrogen Bonding (see also V, paper 1):

1. Znamenskiy, V. S. and Green, M. E. (2004) Topological Changes of Hydrogen Bonding of Water with Acetic Acid: AIM and NBO Studies, J. Phys. Chem. A 108, 6543-6553

2. Znamenskiy, V. S. and Green, M.E. (2007) Quantum Calculations on Hydrogen Bonds in Certain Water Clusters Show Cooperative Effects, J. Chem. Theory and Comp. 3,103-114

VII. The cavity in the channel pore
1. Kariev, A. M. and Green, M. E. (2008) Quantum mechanical calculations on selectivity in the KcsA channel: the role of the aqueous cavity J. Phys. Chem. B 112, 1293-1298
2.  Kariev, A. M. and Green, M. E. (2009) Quantum calculations on water in the KcsA channel cavity with permeant and non-permeant ions  Biochim. Biophys. Acta (Biomemb) 1788, 1188-1192