The prediction of the structure and function of biological macromolecules (i.e., the machinery of life) is of foremost importance in the field of structural biology. Since the elucidation of the three-dimensional structure of DNA (the molecule that carries all genetic information) by Watson and Crick, scientists have strived to decipher the hidden code that determines the evolution of the spatial arrangement of these molecules towards their functional native state. Attempts to follow these structural transitions experimentally and with atomic resolution are hampered by the ultra-fast nature of the folding process. To date, the characterization of these processes by pure computational means has also been very challenging, since monitoring the folding of nucleic acid with realistic methods requires years of computing time in a regular PC.
The researchers Modesto Orozco, Life Sciences Director of the Barcelona Supercomputing Center and responsible of the Molecular Modelling and Bioinformatics group at the Institute for Research in Biomedicine (IRB Barcelona), and Guillem Portella, postdoctoral researcher of his group, have been able to describe for the first time the folding process of a small DNA hairpin in water and with atomic resolution. The study reveals that, unexpectedly, the folding process appears as a competition between different fast folding and slow folding routes, and that microscopic details determine in a random fashion which route is explored. This investigation, conducted by means of molecular dynamics techniques, has been possible thanks to the enormous computing power of the MareNostrum supercomputer.
The present study has far-reaching implications not only because it represents a new milestone in the theoretical study of nucleic acids' folding, but also it is of great importance for the design of new therapeutic strategies based on oligonucleotides. This is the case, e.g., for RNA interference based treatments, which will help to fight complex diseases such as cancer.
The results of the study by Orozco and Portella have been published in the world's leading chemistry magazine, Angewandte Chemie.
Multiple Routes to Characterize the Folding of a Small DNA Hairpin. Guillem Portella and Modesto Orozco.
Angewandte Chemie (2010). doi: 10.1002/ange. 201003816
Angewandte Chemie - International Edition (2010) doi: 10.1002/anie. 201003816