Molecular Dynamics Simulations of the TrkH Membrane Protein

Carmen Domene Nunez, Simone Furini

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

TrkH is a transmembrane protein that mediates uptake of K+ through the cell membrane. Despite the recent determination of its crystallographic structure, the nature of the permeation mechanism is still unknown, that is, whether K+ ions move across TrkH by active transport or passive diffusion. Here, molecular dynamics simulations and the umbrella sampling technique have been employed to shed light on this question. The existence of binding site S3 and two alternative binding sites have been characterized. Analysis of the coordination number renders values that are almost constant, with a full contribution from the carbonyls of the protein only at S3. This observation contrasts with observations of K+ channels, where the contribution of the protein to the coordination number is roughly constant in all four binding sites. An intramembrane loop is found immediately after the selectivity filter at the intracellular side of the protein, which obstructs the permeation pathway, and this is reflected in the magnitude of the energy barriers.
Original languageEnglish
Pages (from-to)1559-1565
Number of pages7
JournalBiochemistry
Volume51
Issue number8
DOIs
Publication statusPublished - 1 Feb 2012

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Molecular Dynamics Simulation
Molecular dynamics
Membrane Proteins
Binding Sites
Computer simulation
Permeation
Proteins
Active Biological Transport
Energy barriers
Cell membranes
Cell Membrane
Ions
Sampling

Keywords

  • POTASSIUM CHANNELS, SELECTIVITY FILTER, FREE-ENERGY, ION CONDUCTION, K+-CHANNELS, PERMEATION, WATER, ENERGETICS, MECHANISM, MODELS

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Molecular Dynamics Simulations of the TrkH Membrane Protein. / Domene Nunez, Carmen; Furini, Simone.

In: Biochemistry, Vol. 51, No. 8, 01.02.2012, p. 1559-1565.

Research output: Contribution to journalArticle

Domene Nunez, Carmen ; Furini, Simone. / Molecular Dynamics Simulations of the TrkH Membrane Protein. In: Biochemistry. 2012 ; Vol. 51, No. 8. pp. 1559-1565.
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