Single-Coordinate-Driving Method Coupled with Simulated Annealing. An Efficient Tool To Search Conformational Space

A single-strand AUG RNA trimer has been studied by computational tools using a single internal coordinate driving method incorporated in the CICADA program interfaced with AMBER molecular mechanics. CICADA, previously appearing a good tool for the global description of the small and middle-sized flexible organic molecules conformational space, failed in this particular case, giving the best minimum of 10 kcal/mol higher than molecular dynamics. We then combined the single-coordinate-driving (SCD) method with simulated annealing (SA), obtaining a global minimum substantially better than that from both CICADA and molecular dynamics. In addition, an interconversion path between both minima has been revealed.The new global minimum exhibits violation of stacking at the G terminal as reported in the experimental data. In comparison with the data obtained by other methods and reported in the literature, the new method yields better results. Additionally, the new method is able to find pathways of conformational interconversions connecting distant parts of the conformational space. The method is now implemented in the updated version of the CICADA program. The results have confirmed that even the PES of such a relatively small molecule exhibits a large number of local minima and that a clustering of the minima into conformational families appears necessary.