Particle Smoother to Assimilate Asynchronous Movie Data of High-Speed AFM with MD Simulations.

Abstract

High-speed (HS) atomic force microscopy (AFM) can be used to observe structural dynamics of biomolecules under near-physiological conditions. In the AFM measurement, the probe tip scans an area of interest and acquires height data pixel by pixel so that the obtained AFM image contains a measurement time difference. In this study, to integrate molecular dynamics simulations with asynchronous HS-AFM movie data, we developed a particle smoother (PS) method for Bayesian data assimilation, one of the machine learning approaches, by extending the previous particle filter method. With a twin experiment with an asynchronous pseudo HS-AFM movie of a nucleosome, we found that the PS method with the pixel-by-pixel data acquisition reproduced the dynamic behavior of a nucleosome better than the previous particle filter method that ignored the data asynchronicity. We examined several frequencies of particle resampling in the PS method, and found that resampling once per one frame was optimal for reproducing the dynamic behavior. Thus, we found that the PS method with an appropriate resampling frequency is a powerful method for estimating the dynamic behavior of a target molecule from HS-AFM data with low spatiotemporal resolution.