The ability of the Amber ff99 force field to predict relative free energies of RNA helix formation was investigated. The test systems were three hexaloop RNA hairpins with identical loops and varying stems. The potential of mean force of stretching the hairpins from the native state to an extended conformation was calculated with umbrella sampling. Because the hairpins have identical loop sequence, the differences in free energy changes are only from the stem composition. The Amber ff99 force field was able to correctly predict the order of stabilities of the hairpins, although the magnitude of the free energy change is larger than that determined by optical melting experiments. The two measurements cannot be compared directly because the unfolded state in the optical melting experiments is a random coil, while the end state in the umbrella sampling simulations was an elongated chain. The calculations can be compared to reference data by using a thermodynamic cycle. By applying the thermodynamic cycle to the transitions between the hairpins using simulations and nearest neighbor data, agreement was found to be within the sampling error of simulations, thus demonstrating that ff99 force field is able to accurately predict relative free energies of RNA helix formation.

Molecular mechanics with all-atom models was used to understand the conformational preference of tandem guanine-adenine (GA) noncanonical pairs in RNA. These tandem GA pairs play important roles in determining stability, flexibility, and structural dynamics of RNA tertiary structures. Previous solution structures showed that these tandem GA pairs adopt either imino (cis Watson–Crick/Watson–Crick A-G) or sheared (trans Hoogsteen/sugar edge A-G) conformations depending on the sequence and orientation of the adjacent closing base pairs. The solution structures (GCGGACGC)2 [Biochemistry, 1996, 35, 9677–9689] and (GCGGAUGC)2 [Biochemistry, 2007, 46, 1511–1522] demonstrate imino and sheared conformations for the two central GA pairs, respectively. These systems were studied using molecular dynamics and free energy change calculations for conformational changes, using umbrella sampling. For the structures to maintain their native conformations during molecular dynamics simulations, a modification to the standard Amber ff10 force field was required, which allowed the amino group of guanine to leave the plane of the base [J. Chem. Theory Comput., 2009, 5, 2088–2100] and form out-of-plane hydrogen bonds with a cross-strand cytosine or uracil. The requirement for this modification suggests the importance of out-of-plane hydrogen bonds in stabilizing the native structures. Free energy change calculations for each sequence demonstrated the correct conformational preference when the force field modification was used, but the extent of the preference is underestimated.

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We present the ultrafast (THz-bandwidth) photoresponse from GaAs single-crystal mesoscopic structures, such as freestanding whiskers and platelets fabricated by the top-down technique, transferred onto a substrate of choice, and incorporated into a coplanar strip line. We recorded electrical transients as short as ∼600 fs from an individual whisker photodetector. Analysis of the frequency spectrum of the photoresponse electrical signal showed that, intrinsically, our device was characterized by an ∼150-fs carrier lifetime and an overall 320-fs response. The corresponding 3-dB frequency bandwidth was 1.3 THz—the highest bandwidth ever reported for a GaAs-based photodetector. Simultaneously, as high-quality, epitaxially grown crystals, our GaAs structures exhibited mobility values as high as ∼7300 cm2/V·s, extremely low dark currents, and ∼7% intrinsic detection efficiency, which, together with their experimentally measured photoresponse repetition time of ∼1 ps, makes them uniquely suitable for terahertz-frequency optoelectronic applications, ranging from ultrafast photon detectors and counters to THz-bandwidth optical-to-electrical transducers and photomixers.