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Modelling DNA under protein-binding, stretching and torsional stress

Banff International Research Station for Mathematical Innovation and Discovery

<p class=Standard><span lang=EN-GB>In vivo, DNA is subjected to torsional and stretching stress due to different cellular processes like protein binding, transcription and replication, that are capable of distorting DNA structure beyond its helicoidal shape. On one hand, DNA is subjected to a supercoiling stress that coils the <span class=SpellE>fiber</span> around itself and opens the double helix facilitating the formation of melting bubbles. On the other hand, different proteins like the TATA-binding protein and the recombinase enzyme <span class=SpellE>RecA</span> can overstretch DNA up till 40% beyond its contour length. In this workshop I will show which are the effect of these disturbing factors on the molecule of DNA through the use of molecular dynamics simulations at atomic level.</span></p> <p class=Standard><span lang=EN-GB>For analysing DNA dynamics due to thermal fluctuation, my team is developing <span class=SpellE>SerraNA</span>, which is a program that calculates the overall elastic constants of DNA from ensembles obtained by molecular simulations [1]. In addition, we also performed simulations on overstretching DNA within the biological regime: up to 40% on extension and within the <i style='mso-bidi-font-style:normal'>in vivo</i> range of supercoiling density) exhibit the capacity of the molecule to present melting bubbles independently to torsional stress, even on positively supercoiled DNA [2]. <a name="_Hlk2171941"></a></span></p> <p class=Standard><span lang=EN-GB>In parallel, <span class=SpellE>torsionally</span>-stressed DNA minicircles are being studied by a combination of high-resolution AFM experiments and atomistic simulations, describing for the first time the structural details of supercoiled DNA at a sub-helical scale [3]. Finally, the DNA-bending IHF protein is embedded on the same type of DNA minicircles for analysing its effect on the global and local shape [4].</span></p> <p class=Standard style='margin-left:14.15pt;text-indent:-14.15pt'><span lang=EN-GB>1. Noy et al, <span class=StrongEmphasis><i><span style='font-weight: normal'>Phys Rev Lett</span></i></span><i>,</i> (2012), 109, 228101.</span></p> <p class=Standard style='margin-left:14.15pt;text-indent:-14.15pt'><span lang=EN-GB>2. Shepherd, Noy and <span class=SpellE>Leake</span> <i style='mso-bidi-font-style:normal'>et al,</i> <span class=StrongEmphasis><i><span style='font-weight:normal'>In preparation</span></i></span></span></p> <p class=Standard style='margin-left:14.15pt;text-indent:-14.15pt'><span lang=EN-GB>3. <span class=SpellE>Pyne</span>, Noy, Main, Velasco, <span class=SpellE>Mitchenall</span>, <span class=SpellE><span style='mso-bidi-font-style: italic'>Cugliandolo</span></span><span style='mso-bidi-font-style:italic'>, <span class=SpellE>Piperakis</span>, Stevenson</span>, <span class=SpellE>Hoogenboom</span>, Bates, Maxwell and Harris, <i style='mso-bidi-font-style:normal'>In preparation<o:p></o:p></i></span></p> <p class=Standard style='margin-left:14.15pt;text-indent:-14.15pt'><span lang=EN-GB>4. Watson, <span class=SpellE>Guilbau</span>, <span class=SpellE>Yoshua</span>, Fogg, <span class=SpellE>Zechiedrich</span>, <span class=SpellE>Leake</span> and Noy, <i style='mso-bidi-font-style:normal'>In preparation</i></span></p>

Mathematics; Biology and other natural sciences; Manifolds and cell complexes; Mathematical biology

video/mp4

Author affiliation: University of York

2019-09-25

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/71768

Unreviewed

http://creativecommons.org/licenses/by-nc-nd/4.0/