The future of biomolecular simulation in the pharmaceutical industry: what we can learn from aerodynamics modelling and weather prediction. Part 1. understanding the physical and computational complexity of in silico drug design.

The predictive power of simulation has become embedded in the infrastructure of modern economies. Computer-aided design is ubiquitous throughout industry. In aeronautical engineering, built infrastructure and materials manufacturing, simulations are routinely used to compute the performance of potential designs before construction.

Single-molecule fluorescence resonance energy transfer assays reveal heterogeneous folding ensembles in a simple RNA stem-loop.

We have examined the folding ensembles present in solution for a series of RNA oligonucleotides that encompass the replicase translational operator stem-loop of the RNA bacteriophage MS2. Single-molecule (SM) fluorescence assays suggest that these RNAs exist in solution as ensembles of differentially base-paired/base-stacked states at equilibrium. There are two distinct ensembles for the wild-type sequence, implying the existence of a significant free energy barrier between "folded" and "unfolded" ensembles.

Modelling the biomechanical properties of DNA using computer simulation.

Duplex DNA must remain stable when not in use to protect the genetic material. However, the two strands must be separated whenever genes are copied or expressed to expose the coding strand for synthesis of complementary RNA or DNA bases. Therefore, the double stranded structure must be relatively easy to take apart when required.