MATHEMATICAL TREATMENTS THAT SOLVE SINGLE MOLECULES
Abstract
In this article, we talk about the ways that scientists can solve single molecule trajectories. Solving single molecules, that is, finding the model from the data, is complicated at least as much as measuring single molecules. We must filter the noise and take care of every step in the analysis when constructing the most accurate model from the data. Here, we present valuable solutions. Ways that solve clean discrete data are first presented. We review here our reduced dimensions forms (RDFs): unique models that are canonical forms of discrete data, and the statistical and numerical toolbox that builds a RDF from finite, clean, two-state data. We then review our most recent filter that "tackles" the noise when measuring two state noisy photon trajectories. The filter is a numerical algorithm with various special statistical treatments that is based on a general likelihood function that we have developed recently. We show the strengths of the filter (also over other approaches) and talk about its various new variants. This filter (with minor adjustments) can solve the noise in any discrete state trajectories, yet, extensions are needed in "tackling" the noise from other data, e.g. continuous data. Only the combined procedures enable creating the most accurate model from noisy discrete trajectories from single molecules. These concepts and methods (with adjustments) are valuable also when solving continuous trajectories and fluorescence resonance energy transfer trajectories. We also present a set of simple methods that can help any scientist with treating the trajectory perhaps encouraging applying the involved methods. The involved methods will appear in software that we are developing now, helping therefore the experimentalists utilizing these methods on real data. Comparisons with other known methods in this field are made.
Special Issue Comment: This article about mathematical treatments when solving single molecules is related to the reviews in this Special Issue about measuring enzymes67 and about FRET experiments2 and about the software QUB.6