TY - JOUR
T1 - How environment supports a state
T2 - Molecular dynamics simulations of two states in bacteriorhodopsin suggest lipid and water compensation
AU - Jang, Hyunbum
AU - Crozier, Paul S.
AU - Stevens, Mark J.
AU - Woolf, Thomas B.
N1 - Funding Information:
Sandia is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company for the United States Department of Energy’s National Nuclear Security Administration under contract DE-AC04-94AL85000. The work at Johns Hopkins University was supported under a grant from the American Cancer Society with contract ACS-RSG-01-048-01-GMC to T.B.W.
PY - 2004/7
Y1 - 2004/7
N2 - The light-driven proton pump bacteriorhodopsin (bR) is a transmembrane protein that uses large conformational changes for proton transfer from the cytoplasmic to the extracellular regions. Crystal structures, due to their solvent conditions, do not resolve the effect of lipid molecules on these protein conformational changes. To begin to understand the molecular details behind such large conformational changes, we simulated two conformations of wild-type bacteriorhodopsin, one of the dark-adapted state and the second of an intermediate (MO) state, each within an explicit dimyristoyl- phosphatidylcholine (DMPC) lipid bilayer. The simulations included all-hydrogen and all-atom representations of protein, lipid, and water and were performed for 20 ns. We investigate the equilibrium properties and the dynamic motions of the two conformations in the lipid setting. We note that the conformational state of the Mo intermediate bR remains markedly different from the dark-adapted bR state in that the Mo intermediate shows rearrangement of the cytoplasmic portions of helices C, F, and G, and nearby loops. This difference in the states remained throughout the simulations, and the results are stable on the molecular dynamics timescale and provide an illustration of the changes in both lipid and water that help to stabilize a particular state. Our analysis focuses on how the environment adjusts to these two states and on how the dynamics of the helices, loops, and water molecules can be related to the pump mechanism of bacteriorhodopsin. For example, water generally behaves in the same manner on the extracellular sides of both simulations but is decreased in the cytoplasmic region of the Mo intermediate. We suspect that the different water behavior is closely related to the fluctuations of microcavities volume in the protein interior, which is strongly coupled to the collective motion of the protein. Our simulation result suggests that experimental observation can be useful to verify a decreased number of waters in the cytoplasmic regions of the late-intermediate stages by measuring the rate of water exchange with the interior of the protein.
AB - The light-driven proton pump bacteriorhodopsin (bR) is a transmembrane protein that uses large conformational changes for proton transfer from the cytoplasmic to the extracellular regions. Crystal structures, due to their solvent conditions, do not resolve the effect of lipid molecules on these protein conformational changes. To begin to understand the molecular details behind such large conformational changes, we simulated two conformations of wild-type bacteriorhodopsin, one of the dark-adapted state and the second of an intermediate (MO) state, each within an explicit dimyristoyl- phosphatidylcholine (DMPC) lipid bilayer. The simulations included all-hydrogen and all-atom representations of protein, lipid, and water and were performed for 20 ns. We investigate the equilibrium properties and the dynamic motions of the two conformations in the lipid setting. We note that the conformational state of the Mo intermediate bR remains markedly different from the dark-adapted bR state in that the Mo intermediate shows rearrangement of the cytoplasmic portions of helices C, F, and G, and nearby loops. This difference in the states remained throughout the simulations, and the results are stable on the molecular dynamics timescale and provide an illustration of the changes in both lipid and water that help to stabilize a particular state. Our analysis focuses on how the environment adjusts to these two states and on how the dynamics of the helices, loops, and water molecules can be related to the pump mechanism of bacteriorhodopsin. For example, water generally behaves in the same manner on the extracellular sides of both simulations but is decreased in the cytoplasmic region of the Mo intermediate. We suspect that the different water behavior is closely related to the fluctuations of microcavities volume in the protein interior, which is strongly coupled to the collective motion of the protein. Our simulation result suggests that experimental observation can be useful to verify a decreased number of waters in the cytoplasmic regions of the late-intermediate stages by measuring the rate of water exchange with the interior of the protein.
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U2 - 10.1529/biophysj.104.039602
DO - 10.1529/biophysj.104.039602
M3 - Article
C2 - 15240452
AN - SCOPUS:3042730827
SN - 0006-3495
VL - 87
SP - 129
EP - 145
JO - Biophysical journal
JF - Biophysical journal
IS - 1
ER -