title: Single molecule conformational memory extraction: p5ab RNA hairpin.
abstract: Extracting kinetic models from single molecule data is an important route to mechanistic insight in biophysics, chemistry, and biology. Data collected from force spectroscopy can probe discrete hops of a single molecule between different conformational states. Model extraction from such data is a challenging inverse problem because single molecule data are noisy and rich in structure. Standard modeling methods normally assume (i) a prespecified number of discrete states and (ii) that transitions between states are Markovian. The data set is then fit to this predetermined model to find a handful of rates describing the transitions between states. We show that it is unnecessary to assume either (i) or (ii) and focus our analysis on the zipping/unzipping transitions of an RNA hairpin. The key is in starting with a very broad class of non-Markov models in order to let the data guide us toward the best model from this very broad class. Our method suggests that there exists a folding intermediate for the P5ab RNA hairpin whose zipping/unzipping is monitored by force spectroscopy experiments. This intermediate would not have been resolved if a Markov model had been assumed from the onset. We compare the merits of our method with those of others.
authors.affiliation: Department of Physics, Indiana University-Purdue University , Indianapolis, Indiana 46202, United States.
authors.forename: Steve
authors.initials: S
authors.lastname: Pressé
authors.forename: Jack
authors.initials: J
authors.lastname: Peterson
authors.forename: Julian
authors.initials: J
authors.lastname: Lee
authors.forename: Phillip
authors.initials: P
authors.lastname: Elms
authors.forename: Justin L
authors.initials: JL
authors.lastname: MacCallum
authors.forename: Susan
authors.initials: S
authors.lastname: Marqusee
authors.forename: Carlos
authors.initials: C
authors.lastname: Bustamante
authors.forename: Ken
authors.initials: K
authors.lastname: Dill
mesh_terms: D000465:Algorithms; D008962:Models, Theoretical; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D012313:RNA / Q000737:chemistry*
chemical_list: D012313:RNA