Nanopore Force Spectroscopy: Insights from Molecular Dynamics Simulations - Nanopores: Sensing and Fundamental Biological Interactions - page 344

often referred to as Steered Molecular Dynamics (SMD) [ 44 , 45 ]. A diagram of how
the forces were applied is shown in Fig. 14.3a . Figure 14.3b shows that the time until
rupture decreased with the loading rate. An advantage of these SMD simulations is
that the force on the virtual springs can be directly and unambiguously extracted.
Figure 14.3c shows the force as a function of time for each of the SMD simulations.
In all cases, the maximum value of the force was observed within a few hundred
picoseconds of the time at which the displacement between the enzyme and DNA
rapidly increased. The SMD simulations enabled us to determine the maximum
force as a function of the loading rate, which is plotted in the inset of Fig. 14.3c .

Fig. 14.3 SMD simulations of restriction enzyme-DNA rupture at different loading rates.
(a) Schematic of the forces applied in the MD simulations. The center of mass of the 10 basepair
fragment of DNA is attached to one end of a virtual spring, whose other end is moved to the right at
a constant velocity. The -carbons of the enzyme are also attached to virtual springs (constraining

force) to keep the enzyme fixed. The portion of the DNA to which the Eco RI binds specifically is
shown in white .(b) The distance between the Eco RI and the DNA vs. time for SMD simulations
at different pulling rates. (c) Force restraining the enzyme as a function of time. The forces are
averaged over 0.5, 0.3, 0.2, and 0.2 ns intervals for loading rates of 0.5, 1.0, 2.5, and 5.0 nm/ns.
The inset shows the force at rupture f ∗ as a function of the loading rate r . The data can be fit
by f ∗ /(1 nN)

a

¼ 1 : 710 þ 0 : 364 ln ðrÞ . Figure adapted from [ 22 ] by permission of the American

Chemical Society