TY - JOUR
T1 - Exploring transmembrane transport through α -hemolysin with grid-steered molecular dynamics
AU - Wells, David B.
AU - Abramkina, Volha
AU - Aksimentiev, Aleksei
N1 - Funding Information:
This work was supported by the grants from the National Institutes of Health (PHS 5 P41 RR05969 and R01-HG003713), and the Department of Physics at the University of Illinois. The authors gratefully acknowledge supercomputer time at the Pittsburgh Supercomputer Center and the National Center for Supercomputing Applications provided via the Large Resources Allocation Committee Grant No. MCA05S028, as well as time on the Turing cluster at the University of Illinois.
PY - 2007
Y1 - 2007
N2 - The transport of biomolecules across cell boundaries is central to cellular function. While structures of many membrane channels are known, the permeation mechanism is known only for a select few. Molecular dynamics (MD) is a computational method that can provide an accurate description of permeation events at the atomic level, which is required for understanding the transport mechanism. However, due to the relatively short time scales accessible to this method, it is of limited utility. Here, we present a method for all-atom simulation of electric field-driven transport of large solutes through membrane channels, which in tens of nanoseconds can provide a realistic account of a permeation event that would require a millisecond simulation using conventional MD. In this method, the average distribution of the electrostatic potential in a membrane channel under a transmembrane bias of interest is determined first from an all-atom MD simulation. This electrostatic potential, defined on a grid, is subsequently applied to a charged solute to steer its permeation through the membrane channel. We apply this method to investigate permeation of DNA strands, DNA hairpins, and α -helical peptides through α -hemolysin. To test the accuracy of the method, we computed the relative permeation rates of DNA strands having different sequences and global orientations. The results of the G-SMD simulations were found to be in good agreement in experiment.
AB - The transport of biomolecules across cell boundaries is central to cellular function. While structures of many membrane channels are known, the permeation mechanism is known only for a select few. Molecular dynamics (MD) is a computational method that can provide an accurate description of permeation events at the atomic level, which is required for understanding the transport mechanism. However, due to the relatively short time scales accessible to this method, it is of limited utility. Here, we present a method for all-atom simulation of electric field-driven transport of large solutes through membrane channels, which in tens of nanoseconds can provide a realistic account of a permeation event that would require a millisecond simulation using conventional MD. In this method, the average distribution of the electrostatic potential in a membrane channel under a transmembrane bias of interest is determined first from an all-atom MD simulation. This electrostatic potential, defined on a grid, is subsequently applied to a charged solute to steer its permeation through the membrane channel. We apply this method to investigate permeation of DNA strands, DNA hairpins, and α -helical peptides through α -hemolysin. To test the accuracy of the method, we computed the relative permeation rates of DNA strands having different sequences and global orientations. The results of the G-SMD simulations were found to be in good agreement in experiment.
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U2 - 10.1063/1.2770738
DO - 10.1063/1.2770738
M3 - Article
C2 - 17902937
AN - SCOPUS:34848830419
SN - 0021-9606
VL - 127
JO - Journal of Chemical Physics
JF - Journal of Chemical Physics
IS - 12
M1 - 125101
ER -