Bayesian analysis of time series of single RNA under fluctuating force

Abstract

Extracting the intrinsic kinetic information of biological molecule from its single-molecule kinetic data is of considerable biophysical interest. In this work, we theoretically investigate the feasibility of inferring single RNA's intrinsic kinetic parameters from the time series obtained by forced folding/unfolding experiment done in the light tweezer, where the molecule is flanked by long double-stranded DNA/RNA handles and tethered between two big beads. We first construct a coarse-grain physical model of the experimental system. The model has captured the major physical factors: the Brownian motion of the bead, the molecular structural transition, and the elasticity of the handles and RNA. Then based on an analytic solution of the model, a Bayesian method using Monte Carlo Markov Chain is proposed to infer the intrinsic kinetic parameters of the RNA from the noisy time series of the distance or force. Because the force fluctuation induced by the Brownian motion of the bead and the structural transition can significantly modulate the transition rates of the RNA, we prove that, this statistic method is more accurate and efficient than the conventional histogram fitting method in inferring the molecule's intrinsic parameters.