Bayesian hidden Markov model analysis of single-molecule force spectroscopy: Characterizing kinetics under measurement uncertainty

Details Bayesian hidden Markov model analysis of single-molecule force spectroscopy: Characterizing kinetics under measurement uncertainty Bayesian hidden Markov model analysis of single-molecule force spectroscopy: Characterizing kinetics under measurement uncertainty

2011-08-06

arxiv.org/abs/1108.1430v1

Physics

Condensed Matter

Statistical Mechanics

Scientific paper

Single-molecule force spectroscopy has proven to be a powerful tool for studying the kinetic behavior of biomolecules. Through application of an external force, conformational states with small or transient populations can be stabilized, allowing them to be characterized and the statistics of individual trajectories studied to provide insight into biomolecular folding and function. Because the observed quantity (force or extension) is not necessarily an ideal reaction coordinate, individual observations cannot be uniquely associated with kinetically distinct conformations. While maximum-likelihood schemes such as hidden Markov models have solved this problem for other classes of single-molecule experiments by using temporal information to aid in the inference of a sequence of distinct conformational states, these methods do not give a clear picture of how precisely the model parameters are determined by the data due to instrument noise and finite-sample statistics, both significant problems in force spectroscopy. We solve this problem through a Bayesian extension that allows the experimental uncertainties to be directly quantified, and build in detailed balance to further reduce uncertainty through physical constraints. We illustrate the utility of this approach in characterizing the three-state kinetic behavior of an RNA hairpin in a stationary optical trap.

Affiliated with

Also associated with

No associations

Rating

Bayesian hidden Markov model analysis of single-molecule force spectroscopy: Characterizing kinetics under measurement uncertainty does not yet have a rating. At this time, there are no reviews or comments for this scientific paper.

If you have personal experience with Bayesian hidden Markov model analysis of single-molecule force spectroscopy: Characterizing kinetics under measurement uncertainty, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Bayesian hidden Markov model analysis of single-molecule force spectroscopy: Characterizing kinetics under measurement uncertainty will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFWR-SCP-O-1251