Amplitude and frequency spectra of thermal fluctuations of a translocating RNA molecule.

Using a combination of theory and computer simulations, we study the translocation of an RNA molecule, pulled through a solid-state nanopore by an optical tweezer, as a method for determining its secondary structure. The resolution with which the elements of the secondary structure can be determined is limited by thermal fluctuations. We present a detailed study of these thermal fluctuations, including the frequency spectrum, and show that these rule out single-nucleotide resolution under the experimental conditions which we simulated. Two possible ways to improve this resolution are strongly stretching the RNA with a back-pulling voltage across the membrane, and stiffening the translocated part of the RNA by biochemical means.

Activated sampling in complex materials at finite temperature: the properly obeying probability activation-relaxation technique.

While the dynamics of many complex systems is dominated by activated events, there are very few simulation methods that take advantage of this fact. Most of these procedures are restricted to relatively simple systems or, as with the activation-relaxation technique (ART), sample the conformation space efficiently at the cost of a correct thermodynamical description. We present here an extension of ART, the properly obeying probability ART (POP-ART), that obeys detailed balance and samples correctly the thermodynamic ensemble. Testing POP-ART on two model systems, a vacancy and an interstitial in crystalline silicon, we show that this method recovers the proper thermodynamical weights associated with the various accessible states and is significantly faster than molecular dynamics in the simulations of a vacancy below 700 K.