TY - JOUR T1 - Direct detection of molecular intermediates from first-passage times JF - bioRxiv DO - 10.1101/772830 SP - 772830 AU - Alice L. Thorneywork AU - Jannes Gladrow AU - Yujia Qing AU - Marc Rico-Pasto AU - Felix Ritort AU - Hagan Bayley AU - Anatoly B. Kolomeisky AU - Ulrich F. Keyser Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/09/19/772830.abstract N2 - All natural phenomena are governed by energy landscapes. However, the direct measurement of this fundamental quantity remains challenging, particularly in complex systems involving intermediate states. Here, we uncover key details of the energy landscapes that underpin a range of experimental systems through quantitative analysis of first-passage time distributions. By combined study of colloidal dynamics in confinement, transport through a biological pore and the folding kinetics of DNA hairpins, we demonstrate conclusively how a short-time, power-law regime of the first-passage time distribution universally reflects the number of intermediate states associated with each process, irrespective of the lengthscales, timescales or interactions in the system. We thereby establish a powerful method for investigating the underlying mechanisms of complex molecular processes. ER -