Enhanced diffusion in soft-walled channels with a periodically varying curvature.

The motion of particles along channels of finite width is known to be hindered by either the presence of energy barriers along the channel direction or by variations in the width of the channel in the transverse direction (rugged channel). Remarkably, when both features are present, they can interact to produce a counterintuitive result: adding energy barriers to a rugged channel can enhance the rate of diffusion along it. This is the result of competing energetic and entropic effects. Under the approximation of particles instantaneously in equilibrium in the transverse direction, one can tailor the energy barriers to the ruggedness to recover free diffusion. However, such fine-tuning and potentially restrictive approximations are not necessary to observe an enhanced rate of diffusion as we demonstrate by adding a range of (non-fine-tuned) energy barriers to a channel of sinusoidally varying curvature. Furthermore, this was observed to hold for systems with a finite characteristic timescale for motion in the transverse direction, thus, suggesting that the phenomenon lends itself to be exploited for practical applications.

An effective one-dimensional approach to calculating mean first passage time in multi-dimensional potentials.

Thermally activated escape processes in multi-dimensional potentials are of interest to a variety of fields, so being able to calculate the rate of escape-or the mean first-passage time (MFPT)-is important. Unlike in one dimension, there is no general, exact formula for the MFPT. However, Langer's formula, a multi-dimensional generalization of Kramers's one-dimensional formula, provides an approximate result when the barrier to escape is large. Kramers's and Langer's formulas are related to one another by the potential of mean force (PMF): when calculated along a particular direction (the unstable mode at the saddle point) and substituted into Kramers's formula, the result is Langer's formula. We build on this result by using the PMF in the exact, one-dimensional expression for the MFPT. Our model offers better agreement with Brownian dynamics simulations than Langer's formula, although discrepancies arise when the potential becomes less confining along the direction of escape. When the energy barrier is small our model offers significant improvements upon Langer's theory. Finally, the optimal direction along which to evaluate the PMF no longer corresponds to the unstable mode at the saddle point.

Effective diffusion in one-dimensional rough potential-energy landscapes.

Diffusion in spatially rough, confining, one-dimensional continuous energy landscapes is treated using Zwanzig's proposal, which is based on the Smoluchowski equation. We show that Zwanzig's conjecture agrees with Brownian dynamics simulations only in the regime of small roughness. Our correction of Zwanzig's framework corroborates well with numerical results. A numerical simulation scheme based on our coarse-grained Langevin dynamics offers significant reductions in computational time. The mean first-passage time problem in the case of random roughness is treated. Finally, we address the validity of the separation of length scales assumption for the case of polynomial backgrounds and cosine-based roughness. Our results are applicable to hierarchical energy landscapes such as that of a protein's folding and transport processes in disordered media, where there is clear separation of length scale between smooth underlying potential and its rough perturbation.

Overdamped Brownian dynamics in piecewise-defined energy landscapes.

We study the overdamped Brownian dynamics of particles moving in piecewise-defined potential energy landscapes U(x), where the height Q of each section is obtained from the exponential distribution p(Q)=aßexp(-aßQ), where ß is the reciprocal thermal energy, and a>0. The averaged effective diffusion coefficient 〈D_{eff}〉 is introduced to characterize the diffusive motion: 〈x^{2}〉=2〈D_{eff}〉t. A general expression for 〈D_{eff}〉 in terms of U(x) and p(Q) is derived and then applied to three types of energy landscape: flat sections, smooth maxima, and sharp maxima. All three cases display a transition between subdiffusive and diffusive behavior at a=1, and a reduction to free diffusion as a→∞. The behavior of 〈D_{eff}〉 around the transition is investigated and found to depend heavily upon the shape of the maxima: Energy landscapes made up of flat sections or smooth maxima display power-law behavior, while for landscapes with sharp maxima, strongly divergent behavior is observed. Two aspects of the subdiffusive regime are studied: the growth of the mean squared displacement with time and the distribution of mean first-passage times. For the former, agreement between Brownian dynamics simulations and a coarse-grained equivalent was observed, but the results deviated from the random barrier model's predictions. The discrepancy could be a finite-time effect. For the latter, agreement between the characteristic exponent calculated numerically and that predicted by the random barrier model is observed in the large-amplitude limit.

Dissociation rates from single-molecule pulling experiments under large thermal fluctuations or large applied force.

Theories that are used to extract energy-landscape information from single-molecule pulling experiments in biophysics are all invariably based on Kramers' theory of the thermally activated escape rate from a potential well. As is well known, this theory recovers the Arrhenius dependence of the rate on the barrier energy and crucially relies on the assumption that the barrier energy is much larger than k_{B}T (limit of comparatively low thermal fluctuations). As was shown already in Dudko et al. [Phys. Rev. Lett. 96, 108101 (2006)PRLTAO0031-900710.1103/PhysRevLett.96.108101], this approach leads to the unphysical prediction of dissociation time increasing with decreasing binding energy when the latter is lowered to values comparable to k_{B}T (limit of large thermal fluctuations). We propose a theoretical framework (fully supported by numerical simulations) which amends Kramers' theory in this limit and use it to extract the dissociation rate from single-molecule experiments where now predictions are physically meaningful and in agreement with simulations over the whole range of applied forces (binding energies). These results are expected to be relevant for a large number of experimental settings in single-molecule biophysics.