TY - JOUR
T1 - Atomistic Characterization of Gramicidin Channel Formation
AU - Sun, Delin
AU - He, Stewart
AU - Bennett, W. F.Drew
AU - Bilodeau, Camille L.
AU - Andersen, Olaf S.
AU - Lightstone, Felice C.
AU - Ingólfsson, Helgi I.
N1 - Funding Information:
This work was funded by Laboratory Directed Research and Development at the Lawrence Livermore National Laboratory (18-ERD-035). We thank the Livermore Institutional Grand Challenge for the computing time. This work was performed under the auspices of the U.S. DOE by the Lawrence Livermore National Laboratory under contract DE-AC52-07NA27344. O.S.A. is the recipient of NIH grant R01 GM021342, Release LLNL-JRNL-813847.
Publisher Copyright:
©
PY - 2021/1/12
Y1 - 2021/1/12
N2 - We investigated gramicidin A (gA) subunit dimerization in lipid bilayers using microsecond-long replica-exchange umbrella sampling simulations, millisecond-long unbiased molecular dynamics simulations, and machine learning. Our simulations led to a dimer structure that is indistinguishable from the experimentally determined gA channel structures, with the two gA subunits joined by six hydrogen bonds (6HB). The simulations also uncovered two additional dimer structures, with different gA-gA stacking orientations that were stabilized by four or two hydrogen bonds (4HB or 2HB). When examining the temporal evolution of the dimerization, we found that two bilayer-inserted gA subunits can form the 6HB dimer directly, with no discernible intermediate states, as well as through paths that involve the 2HB and 4HB dimers.
AB - We investigated gramicidin A (gA) subunit dimerization in lipid bilayers using microsecond-long replica-exchange umbrella sampling simulations, millisecond-long unbiased molecular dynamics simulations, and machine learning. Our simulations led to a dimer structure that is indistinguishable from the experimentally determined gA channel structures, with the two gA subunits joined by six hydrogen bonds (6HB). The simulations also uncovered two additional dimer structures, with different gA-gA stacking orientations that were stabilized by four or two hydrogen bonds (4HB or 2HB). When examining the temporal evolution of the dimerization, we found that two bilayer-inserted gA subunits can form the 6HB dimer directly, with no discernible intermediate states, as well as through paths that involve the 2HB and 4HB dimers.
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U2 - 10.1021/acs.jctc.0c00989
DO - 10.1021/acs.jctc.0c00989
M3 - Article
C2 - 33378617
AN - SCOPUS:85099774076
VL - 17
SP - 7
EP - 12
JO - Journal of Chemical Theory and Computation
JF - Journal of Chemical Theory and Computation
SN - 1549-9618
IS - 1
ER -