We propose an approach to help interpret polymer force–extension curves that exhibit plateau regimes. When coupled to a bead–spring dynamic model, the approach accurately reproduces a variety of experimental force–extension curves of long double-stranded DNA and RNA, including torsionally constrained and unconstrained DNA and negatively supercoiled DNA. A key feature of the model is a specific nonconvex energy function of the spring. We provide an algorithm to obtain the five required parameters of the model from experimental force–extension curves. The applicability of the approach to the force–extension curves of double-stranded (ds) DNA of variable GC content as well as to a DNA/RNA hybrid structure is explored and confirmed. We use the approach to explain counterintuitive sequence-dependent trends and make predictions. In the plateau region of the force–extension curves, our molecular dynamics simulations show that the polymer separates into a mix of weakly and strongly stretched states without forming macroscopically distinct phases. The distribution of these states is predicted to depend on the sequence.

Multiple studies have shown a correlation between gene expression and positioning of genes at nuclear envelope (NE) lined by nuclear lamina. Here, we ask whether there is a causal, systematic connection between the expression level of the groups of genes in topologically associating domains (TADs) of Drosophila nuclei and the probability of TADs to be found at the NE. To investigate the connection, we combine a coarse-grained dynamic model of the entire Drosophila nucleus with the genome-wide gene expression data for both the control and lamins depleted (LD) nuclei. We analyze the TAD averaged transcription levels of genes against the probabilities of individual TADs to be near the NE. Our findings suggest that, within statistical error margin, positioning of Drosophila TADs at the nuclear envelope does not, by itself, systematically affect the average gene expression in these TADs, while the expected negative correlation is confirmed. Verifiable hypotheses of the underlying mechanism for the presence of correlation without causality are discussed. We introduce a TAD length normalized metric for the average transcription activity of genes in a TAD: number of Reads mapped to all genes in a TAD Per Kilobase of TAD length per Million reads mapped to all TADs (RPKMT).

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We propose a bead-spring model that accurately reproduces a variety of experimental force-extension curves of long double-stranded DNA and RNA, including torsionally constrained and unconstrained DNA, and negatively supercoiled DNA. A key feature of the model is a specific non-convex energy function of the spring. We provide an algorithm for obtaining five required parameters of the model from experimental force-extension curves. In the plateau region of the force-extension curves, our molecular dynamics simulations show that the polymer separates into a mix of weakly and strongly stretched states without forming macroscopically distinct phases.