## Similar protocols

## Protocol publication

[…] Four systems, namely, A- and
B-form poly-GC and poly-AT DNA molecules,
were generated using the Nucleic Acid Builder (NAB) software package, and the SWNT was generated using TubeGen 3.3., The systems were solvated via **visual** molecular dynamics (VMD), with 22 Na+ ions and TIP3P water to neutralize charge and represent solvent
explicitly with cubic water boxes 80 Å on each side generated
within the MMTSB modeling package using
the CHARMM29 force field., Short-range electrostatics
were truncated at 12 Å with a switching function beginning at
10 Å, while long-range electrostatics were calculated with the
particle mesh Ewald method with a grid
spacing of 1.0 Å and a sixth-order B-spline used for interpolation.
A 2 fs time step was employed with the SHAKE algorithm as implemented in CHARMM to constrain bonds to hydrogens.
The SWNT was placed initially in the same configuration relative to
the DNA as that calculated in the study by Lu et al. (shown in Figure ), who used a
self-consistent charge **density-functional-based** tight-binding method
(SCC-DFTB) to determine energetics, relative
stability, and electronic properties of the complexed system.Each system was minimized
and then heated using Langevin dynamics
and equilibrated for 2 ns, with harmonic constraints placed on heavy
atoms for initial heating and released when the systems completed
the equilibration phase. Harmonic constraints were then placed on
all carbon atoms of the SWNT to hold them in their equilibrated positions,
while another harmonic constraint held the distance between the DNA
center of mass and the SWNT center of mass stable. We adopted the
ΔRMSD metric as our order parameter similar to work done previously
by Banavali and Roux, wherein the metric
was used to study the energetics of B- to A-form DNA transitions.
ΔRMSD is defined as the difference between the RMSDs of an instantaneous
structure relative to two reference structures (the B and the A forms)
(see below). This metric is advantageous as a reaction coordinate
for smooth transitions because it neither forces the system along
one particular reaction pathway nor biases it toward one reference
in particular, but still retains the convenience of a single-order
parameter around which one can constrain with simple harmonic potentials.
In other words, the reaction coordinate structures are allowed to
move around in sample space away from the two end structures, as long
as the difference between RMSD (relative to the end points) is harmonically
restrained in successive i-labeled umbrella potentials
according to the restraint potential energy1where ki is the harmonic force constant
of the ith
restraint and2with r⃗ being the
3N-dimensional configurational vector of the N atoms in the system, and RMSDB = ∥r⃗ – r⃗B∥ and RMSDA = ∥r⃗ – r⃗A∥ where ∥···∥
denotes the 2-norm of the difference of the Cartesian coordinates
of an instantaneous configuration r⃗ with
respect to idealized A- or B-form Cartesian coordinates. In this way
we apply a restraining force involving both A and B forms as reference
structures, using ki as
the force constant and Δρmini as the minimum around
which we constrain the reaction coordinate in the i-th simulation window. The reaction coordinate Δρ is
chosen such that it is a (positive) maximum if the system is in an
A-like conformation, whereas Δρ is a minimum (negative)
when the system is in a B-like conformation (although degenerate extrema
in Δρ exist for non-A or -B forms, according to the geometry
of the underlying multidimensional hyperboloids involved in the definition
of the order parameter). Employing our constraint, Δρ
was restrained from −5 to 5 Å with windows of 0.4 Å
spacing. Each umbrella sampling window was equilibrated for 1 ns,
and each window was initiated from the final coordinates of the previous
window to minimize the value of the energy penalty due to our constraint
from window to window. ΔRMSD for each window was binned as a
histogram, and sufficient overlap between neighboring windows was
accumulated as needed to achieve convergence of the PMF, which was
calculated using the WHAM method., The autocorrelation
function (ACF) of our reaction coordinate Δρ across simulation
time t, C(t) =
⟨Δρ(0)·Δρ(t)⟩
was fitted to a single exponential e–t/τ. The decay time τ was found to be
within a tenth of our simulation time, ensuring convergence of the
metric and allowing for bootstrap error analysis within the WHAM implementation., Although necessary but not sufficient conditions for accuracy, error
margins were found to be small enough to be considered negligible
(data not shown). Furthermore, once the PMF was calculated, additional
windows were run at regular intervals and intercalated between each
previously run window (bringing total window separation to 2 Å),
with little change observed in overall PMF curves, suggesting convergence
of the calculation. […]

## Pipeline specifications

Software tools | VMD, DFTB |
---|---|

Application | Protein structure analysis |

Chemicals | Carbon |