Abstract
BackgroundPlasmid DNA molecules are closed circular molecules that are widely used in life sciences, particularly in gene therapy research. Monte Carlo methods have been used for several years to simulate the conformational behavior of DNA molecules. In each iteration these simulation methods randomly generate a new trial conformation, which is either accepted or rejected according to a criterion based on energy calculations and stochastic rules. These simulation trials are generated using a method based on crankshaft motion that, apart from some slight improvements, has remained the same for many years.ResultsIn this paper, we present a new algorithm for the deformation of plasmid DNA molecules for Monte Carlo simulations. The move underlying our algorithm preserves the size and connectivity of straight-line segments of the plasmid DNA skeleton. We also present the results of three experiments comparing our deformation move with the standard and biased crankshaft moves in terms of acceptance ratio of the trials, energy and temperature evolution, and average displacement of the molecule. Our algorithm can also be used as a generic geometric algorithm for the deformation of regular polygons or polylines that preserves the connections and lengths of their segments.ConclusionCompared with both crankshaft moves, our move generates simulation trials with higher acceptance ratios and smoother deformations, making it suitable for real-time visualization of plasmid DNA coiling. For that purpose, we have adopted a DNA assembly algorithm that uses nucleotides as building blocks.
Highlights
Plasmid DNA molecules are closed circular molecules that are widely used in life sciences, in gene therapy research
To evaluate the effectiveness and performance of our deformation method when applied in Monte Carlo (MC) simulations, we performed a set of experiments comparing our method with two types of DNA chain moves, namely, the standard crankshaft move and the biased crankshaft move
As in the deformation method introduced by Klenin et al [4,5], the biased crankshaft move used here adjusts only the rotation angle
Summary
Plasmid DNA molecules are closed circular molecules that are widely used in life sciences, in gene therapy research. Monte Carlo methods have been used for several years to simulate the conformational behavior of DNA molecules In each iteration these simulation methods randomly generate a new trial conformation, which is either accepted or rejected according to a criterion based on energy calculations and stochastic rules. Plasmid DNA (pDNA) is a family of DNA molecules widely used in life sciences, in gene therapy research These molecules are produced inside host cells in a supercoiled conformation (i.e., their natural conformation), which is the desired conformation for therapy purposes. The Monte Carlo (MC) method has generally been accepted as a reliable tool for simulation purposes, and is seen as the standard This iterative method tries to minimize the elastic energy of the molecule in each iteration step of the simulation process, testing the probability of acceptance of each new trial. The goal is to make the molecule converge to an equilibrium state after performing as few iterations as possible, i.e., maximizing the acceptance ratio of the trials without compromising the effectiveness and reliability of the simulation
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