Molecular dynamics simulations of the TrkH membrane protein.
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.
Physical and Theoretical Chemistry Laboratory, Department of Chemistry, University of Oxford, Oxford OX1 3QZ, UK. carmen.domene@chem.ox.ac.uk
Carmen
C
Domene
Simone
S
Furini
D001665:Binding Sites; D018360:Crystallography, X-Ray; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D014736:Vibrio parahaemolyticus
D026901:Membrane Transport Proteins; D015221:Potassium Channels; D011188:Potassium