Unravelling the Transition Paths during Nucleic Acids and Proteins Folding

As biomolecules such as DNA and proteins fold, they follow certain paths that take them from a disordered state to a folded one throughout transition paths. Using advanced optical tweezer technology and force spectroscopy measurements, the transition-path time distributions during the folding of proteins and nucleic acid, have been measured for the first time yielding data in near-perfect agreement with theory,

Optical tweezers were used to grab each end of a biomolecule while forces were applied to change its folding state. The measurement of the distance between the two ends of the molecule provided the timing and energy of the folding transition. The scientists studied a ‘hairpin’ structure, a basic structural element in single-stranded DNA and RNA. They found that it spent around 30 microseconds in the transition state between folded and unfolded. The prion misfolding process takes much longer, around 500 microseconds.