3.1. Translocation Times and Their Dispersions: (100) Sequences
We measured the number of monomers in the
trans side
to identify translocation times for various solvent conditions characterized by
. If a monomer entered the
trans region (
), it was counted as a translocated monomer. We show the translocation times
for chain length
N = 30 and
N = 90 in
Table 1 and
Figure 3.
The waiting time is the MD time required for the number of trans side monomers to be = 5. The chain does not retreat back once the number of translocated monomers reaches five. This cut off point has been found to be nearly independent of the chain length N. This is consistent with the fact that the retreating force mainly depends on the local structure of the globule and is almost independent of the chain length. In poor solvent conditions, = 5 suffices to ensure nucleation in the trans side. This condition does not depend on the remaining chain length in the cis side. In good or intermediate solvent conditions, the entropic free energy of the chain dangled in the cis side only grows with chain length logarithmically. Hence, the free energy barrier to enter the pore has very weak N dependence, so the cut-off point remains nearly constant. In our model, is a discrete variable, and every third monomer carries a charge. This periodicity suppresses the weak variation in the cut-off point that is expected in a continuous model.
After
, the time until the tail of the chain leaves the channel is the drift time
. The total translocation time
is the sum of
and
(See
Figure 4). The waiting time
shows stronger solvent condition dependence than
, which is mainly determined by the chain length. The overall translocation time
increases with increasing
values for
, together with relative standard deviation. In the driven regime,
increases with time (step-wise) linearly with some fluctuations of ∼
. For very poor solvent conditions,
, the process accelerates at late times, which implies the formation of stable globules in the
trans side. Some movie files are available in
Supplementary Materials. Consistent with the results restricted to homopolymers [
20], we found that the translocation time at good solvent (e.g.,
= 0.1) or theta solvent (e.g.,
= 0.3) conditions was somewhat longer than that in weakly poor solvent conditions (e.g.,
= 0.5) because the PE was not globular yet and did not need to be uncoiled. The PE at
= 0.5 was slightly more compact than at
= 0.3, and the entropic force against translocation was smaller. In contrast to the results reported for homopolymers [
20], the minimum in the translocation time at a weakly poor solvent condition was very shallow, and, for moderate hydrophobicity, the translocation time appeared almost independent of
. After the shallow minimum, the translocation time markedly increased with hydrophobicity. Given that we considered a regular PE, the dispersion in translocation times remained moderate (See
Figure 3d).
The entropic penalty is against the engagement of the PE toward the narrow channel. In good solvent conditions, the electrostatic driving force
should be balanced by the entropic force at the start. At the steady state, the net force is balanced by friction,
. As translocation proceeds, more monomers are accumulated in the
trans side. Then, entropic force is favorable for translocation, and the drift becomes faster. The drift speed is almost constant at
In poor solvent conditions, the globule should unfold in order to engage through the narrow channel. The friction involved in passing through the corrugated channel potential adds up with the internal globule friction upon unwinding. As more and more monomers translocate, the surface tension becomes favorable for translocation and further promotes drift. Upon analyzing the translocation process (See
Figure 5a), we distinguished two regimes: (1) the waiting period and (2) the driven period. The captured chain was waiting for further uncoiling or to overcome entropic force. The waiting period ended when the translocated length reached the sufficient length
(≈ 5).
As shown in
Figure 3 and
Table 1, for the given
N,
moderately increased with
. The effective friction
also increased moderately with increasing
(
Table 2). The simulation data in
Figure 5b is the average of 100 trials after resetting
to
t = 0. The effective friction
reflects the channel friction and internal globule friction, depending on the density of the globular structure. In an early regime of the drift,
grows with time linearly. We extracted the effective friction
from the slope via the relation
and assumed that the driving force
was almost constant. This result for
is summarized in
Table 2.
The slope shows the time dependence of the translocation speed (
Figure 5b). The flat speed in the inset captures the drift regime. For
, the slope
changed as the
trans globule promoted the translocation process at later times, and the effective friction was reduced accordingly. This effect was more evident for larger
. The process accelerated as the imbalance of surface tension contributed as the driving force. The dependence of the translocation speed on
could be interpreted as the change in the effective friction as reported for polymers ejected out from a cavity [
24,
25].
In adopting the HP model of globule, we tried to obtain the friction constant
for the given solvent quality. We assumed that the free energy of the HP globules on the
cis and
trans sides consisted of surface energy and potential energy under the electric field across the channel. With
monomers in the
trans side, the free energy accounting for surface tension and external electric potential is defined as follows:
where
p is the periodicity of the charge sequence. Because the channel is filled, it does not contribute to the free energy variation, and is filled up to fluctuations in monomer and charge content of the channel. In the driven regime, we solved the simplified kinetic equation for
:
We compared the
obtained from simulation and from the numerical solution of the Equation (
2) for
and extracted the prefactor
and
(See
Figure 5). Note that, with
p =3, it happened to be that
was equal to the prefactor of the free energy term in Equation (
1),
. The fitting results for
and
are summarized in
Table 2. The fitted values of
were somewhat smaller than
from the early driven regime. This reflects the nucleation of the trans globule accelerating the translocation. Consistent with the fact that the translocation time
and the drift time
had minimums at
= 0.5, both
and
were smallest for
= 0.5.
We further investigated the influence of the chain length
N on translocation. The measured values are shown in
Figure 3b, and the values at
= 0.9 are summarized in
Table 3. The drift time
increased approximately linearly with
N, and the magnitude of the effective friction coefficient also tended to increase. The waiting time
showed moderate dependence on the chain length
N. The standard deviation remained as large as the average values of
(
Figure 3d).
The effective friction
is related to the relaxation of uncoiling the globule [
26,
27,
28,
29,
30,
31]. We checked the globule structures for
N = 30 and
N = 90 for various values of
. The monomer density correlation function
and density
of
cis side globules are shown in
Appendix A.
As the monomer relaxation time
had a larger value in a polymer melt with a high density [
32,
33], the unit time
was larger in polymer globules with higher density, and, thus, the effective friction coefficient increased with the density of the globules (See
Appendix A). Although the drift regime is well defined on average for most of
, each trajectory of translocation can differ significantly from the average, especially at poor solvent conditions. In
Figure 6, we plotted several typical trajectories of PEs of
N = 90 at
= 0.9. The slow progression of translocation in the drift regime, depicted as plateaus in
trajectories, can be attributed to the slow monomer relaxation in the dense core of the globule as opposed to the P-rich corona (see also Ref. [
10]).
Note that the equilibrated initial
cis side globule has a well optimized free energy and is tougher to uncoil than the fresh-folded
trans side globule. Therefore, the friction upon the folding of the
trans side globule is lower than the friction upon extraction from the equilibrated
cis side globule. Because the local structure and interface (a few monomers in size) relax very fast and the free energy relaxes very fast after/upon folding, the measured density profiles of H- and P-type monomers in the
trans side globules (not shown) are alike with those in the equilibrated
cis side globule (shown in
Appendix A Figure A1). The full intermixing inside the globule between older and newer parts is slower and mainly affects the unwinding friction of the
trans globule (in the case of retraction). The effect of aging on friction would be much stronger for larger entangled globules [
26,
27,
30].
Figure 7 demonstrates mixing degrees of monomers in the
trans and
cis globules. Monomers are colored as blue to red along the contour from head to tail. The mixing of colors is less frequent in the
trans side.
Table 4 summarizes the sequence dependences of translocation times for three sequences: (100)
, (010)
, and (001)
. When the chain started with favorable charge as a head monomer, the capture probability was high. At a good solvent condition of
= 0.3, the translocation probability of (100)
was ∼1, but (001)
translocated with a probability of 0.29. At a poor solvent condition
= 0.9, (100)
had a long waiting time but still had a good success rate of 0.94. In contrast, most of the trials of (001)
were rejected, and successful ones had relatively short translocation times.
3.2. Free Energy Profiles and the Solution of Fokker-Planck Equation
In order to rationalize the solvent-dependent behavior of translocation times, we solved a Fokker–Planck equation for the position of the head monomer. The profile of the potential energy
U can be obtained as a function of the number of monomers,
, residing in the
trans region (
) and pore (
) (i.e.,
). There are mainly three contributions: (a) the channel entropic effect
, (b) electrostatic potential energy
, and (c) surface energy
; the latter is relevant in the poor solvent conditions. The early translocation process
was mainly controlled by
. The reference energy value was taken as the energy in the
cis side. As a monomer engaged into the channel, the free energy increased until the monomer reached the
trans-side channel end, which was mainly due to the entropic penalty, even in the presence of the electric field favorable for translocation. The electrostatic contribution to the free energy decreased by 5.8
per translocated charge. We set the electrostatic potential energy as
= −1.9
m, assuming that 1/3 of monomers were charged (i.e.,
p = 3). The surface energy is calculated as:
In order to obtain a more precise form of the free energy over a wider range of translocation states, especially to cover small
m regions while taking into account the influence of the entropic effect
, we exploited the following simulation to compute the success rate. We counted successful attempts of arrivals at a specific position,
m =
b. As shown in detail in the
Appendix B, the success rate
is related to the potential energy
U by the following equation:
with the fixed (absorbing) boundaries at
and the starting point at
x. The differential of the success rate is
, and the logarithm of the differential of the success rate yields ∼
. In order to get the free energy profile, we evaluates the success rate for various values of
m in a discrete manner. (
Figure 8a) The translocation processes were repeated for
–
times, with the PEs equilibrated with fixed number
m. After taking the logarithm of the difference in success rate,
, we obtained the potential energy
. This approach is generally valid and operational until the top of the (last) barrier
is reached and the measured success rate saturates to 100%. Since the potential energy is mainly given by
and
in the following drift regime, we used the free energy expression
starting from
.
Based on the discrete points obtained, we constructed the potential profiles
using polynomial representation (see
Table 5). To construct effective potentials for Fokker–Planck equations for head monomers, we took the continuum model from the discrete values, which is the number of monomers in the (
z > 0) region. What matters in an FP equation is the height of the barriers. A continuous free energy profile was made to catch the free energy height properly when the head monomer engaged toward the potential. Note that the initial position of the head was set to be at
m = 4, where the head monomer was still confined by the pore. For
m = 5, head monomer was released from the pore across the electric potential to the trans side. There was a small energy barrier against the negatively charged monomers toward the end of channel. (See
Figure 2). The potential values at discrete points were obtained by taking the logarithm of the success rate increment (Equation (
4)). There was discontinuity in our geometric environment between
m = 4 and
m = 5. Therefore, to capture the electrostatic properties of the channel potential, we used two polynomials before and after
= 4.5 in the polynomial expression (
Table 5). The polynomial representations of potentials for various values of
are shown in
Figure 8a. We wanted to describe the polymer under translocation through a Fokker–Planck equation for the motion of the head of the polymer. The translocation system is complex, and its friction depends on the translocated length and excited internal polymer modes. Strictly speaking, the polymer should be described by a (Fokker–Planck) equation in configurational space. The translocating PE is confined in the channel or collapsed into a globule. Except when a strongly fluctuating PE chain section is involved, such as in a good solvent (
= 0.1) or theta solvent condition (
= 0.3) outside the channel, it is legitimate to solve the simple Fokker–Planck equation for the head monomer, which ignores internal modes [
34,
35]. The Fokker–Planck equation with the proper potential is expected to be useful throughout.
The probability to find the head at
y after time
t starting from
x at time
,
, satisfies the homogeneous Fokker–Planck equation:
Because we considered the translocation of the polymer, we set the boundary conditions at the ends of the interval inside, wherein the head of the polymer was constrained to
. The boundary conditions for the translocation are absorbing boundaries at both
a = 0 and
b (=
= 10), which means that, when the head of the polymer reaches the absorbing barrier, it is removed from the system so that the probabilities of being on the boundaries are zero.
Then, the probability,
, of exit through
b is given by Equation (
4), and we find the mean exit time as follows:
The detailed derivation for the translocation times (including higher moments) for the head of the polymer by the Fokker–Planck equation is shown in
Appendix B (See also Ref. [
36]).
A complete picture was also obtained numerically using the Runge–Kutta method, and the results of
and
were consistent with the integral expressions of Equation (
4) and Equation (
7).
Figure 8 and
Table 6 summarize the success rates
and the exit times
obtained from Equations (
4) and (
7), with absorbing boundaries at
a = 0 and
= 10 and with the starting position at
x = 4. In order to compare with the simulation results, the time unit
(
= 1) was multiplied. The results were compared with the waiting time
obtained from simulations, where we set the initial head position at the
trans end (i.e,
m = 4) and the exit boundary to be
m = 0 (rejected) and
m = 10 (
= 5). The two results agreed well for
and started deviating from each other at
.