Vestergaard, C.L. et al. Phys. Rev. E Stat. Nonlin. Soft Matter Phys. 89, 022726 (2014).

A ubiquitous method for estimating the diffusion rate of a particle follows directly from Einstein's observation that particle displacement increases over time in proportion to the diffusion constant and involves simple fitting of a straight line to measured values of the mean-square displacement. Vestergaard et al. show that estimates obtained from a single trajectory using this method are intrinsically correlated and that the precision of an estimated diffusion constant decreases as more data are used to fit the line. They present an alternative estimator that performs better for typical single-molecule data and estimated the diffusion constant of a DNA repair protein moving on DNA. The method should be extendable to two-dimensional diffusion data. Researchers measuring diffusion using a single or limited numbers of particle tracks are advised to examine this alternative estimator.