Influence of a fluorobenzene nucleobase analogue on the conformational flexibility of RNA studied by molecular dynamics simulations

Chemically modified bases are frequently used to stabilize nucleic acids, to study the driving forces for nucleic acid structure formation and to tune DNA and RNA hybridization conditions. In particular, fluorobenzene and fluorobenzimidazole base analogues can act as universal bases able to pair with any natural base and to stabilize RNA duplex formation. Although these base analogues are compatible with an A-form RNA geometry, little is known about the influence on the fine structure and conformational dynamics of RNA. In the present study, nano-second molecular dynamics (MD) simulations have been performed to characterize the dynamics of RNA duplexes containing a central 1'-deoxy-1'-(2,4-difluorophenyl)-ß-D-ribofuranose base pair or opposite to an adenine base. For comparison, RNA with a central uridine:adenine pair and a 1'-deoxy-1'-(phenyl)-ß-D-ribofuranose opposite to an adenine was also investigated. The MD simulations indicate a stable overall A-form geometry for the RNAs with base analogues. However, the presence of the base analogues caused a locally enhanced mobility of the central bases inducing mainly base pair shear and opening motions. No stable ‘base-paired’ geometry was found for the base analogue pair or the base analogue:adenine pairs, which explains in part the universal base character of these analogues. Instead, the conformational fluctuations of the base analogues lead to an enhanced accessibility of the bases in the major and minor grooves of the helix compared with a regular base pair

A comparison of head and manual control for a position-control pursuit tracking task

Head control was compared with manual control in a pursuit tracking task involving proportional controlled-element dynamics. An integrated control/display system was used to explore tracking effectiveness in horizontal and vertical axes tracked singly and concurrently. Compared with manual tracking, head tracking resulted in a 50 percent greater rms error score, lower pilot gain, greater high-frequency phase lag and greater low-frequency remnant. These differences were statistically significant, but differences between horizontal- and vertical-axis tracking and between 1- and 2-axis tracking were generally small and not highly significant. Manual tracking results were matched with the optimal control model using pilot-related parameters typical of those found in previous manual control studies. Head tracking performance was predicted with good accuracy using the manual tracking model plus a model for head/neck response dynamics obtained from the literature