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Velasco-Berrelleza, V.

Publications and source records attributed to Velasco-Berrelleza, V..

2 recordsLinked to original sources
bioRxiv2020

SerraNA: a program to infer elastic constants from local to global using nucleic acids simulation data

The resistance of DNA to stretch, twist and bend is broadly well estimated by experiments and is important for gene regulation and chromosome packing. However, their sequence-dependence and how bulk elastic constants emerge from local fluctuations is less understood. Here, we present SerraNA, which is an open software that calculates elastic parameters of double-stranded nucleic acids from dinucleotide length up to the whole molecule using ensembles from numerical simulations. The program reveals that global bendability emerge from local periodic bending angles in phase with the DNA helicoidal shape. We also apply SerraNA to the whole set of 136 tetra-bp combinations and we observe a high degree of sequence-dependence for all elastic parameters with differences over 200%. Tetramers with TA and CA base-pair steps are especially flexible, while tetramers containing AA and AT tend to be the most rigid. Our results thus suggest AT-rich motifs generate extreme mechanical properties depending of the exact sequence ordering, which seems critical for creating strong global bendability on longer sequences when phased properly. SerraNA is a tool to be applied in the next generation of interdisciplinary investigations to further understand what determines the elasticity of DNA. Graphical TOC Entry O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/004945v2_ufig1.gif" ALT="Figure 1"> View larger version (18K): org.highwire.dtl.DTLVardef@18aa2ddorg.highwire.dtl.DTLVardef@ca5e02org.highwire.dtl.DTLVardef@1e1febeorg.highwire.dtl.DTLVardef@1b772b_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗
bioRxiv2019

Combining high-resolution AFM with MD simulations shows that DNA supercoiling induces kinks and defects that enhance flexibility and recognition.

In the cell, DNA is arranged into highly-organised and topologically-constrained (supercoiled) structures. It remains unclear how this supercoiling affects the detailed double-helical structure of DNA, largely because of limitations in spatial resolution of the available biophysical tools. Here, we overcome these limitations, by a combination of atomic force microscopy (AFM) and atomistic molecular dynamics (MD) simulations, to resolve structures of negatively-supercoiled DNA minicircles at base-pair resolution. We observe that negative superhelical stress induces local variation in the canonical B-form DNA structure by introducing kinks and defects that affect global minicircle structure and flexibility. We probe how these local and global conformational changes affect DNA interactions through the binding of triplex-forming oligonucleotides to DNA minicircles. We show that the energetics of triplex formation is governed by a delicate balance between electrostatics and bonding interactions. Our results provide mechanistic insight into how DNA supercoiling can affect molecular recognition, that may have broader implications for DNA interactions with other molecular species.

biophysics↗