Modelling DNA under protein-binding, stretching and torsional stress

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 fiber 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 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. For analysing DNA dynamics due to thermal fluctuation, my team is developing SerraNA, 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 in vivo range of supercoiling density) exhibit the capacity of the molecule to present melting bubbles independently to torsional stress, even on positively supercoiled DNA [2]. In parallel, torsionally-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 lang=EN-GB>1. Noy et al, <span style='font-weight: normal'>Phys Rev Lett, (2012), 109, 228101. <span lang=EN-GB>2. Shepherd, Noy and Leake <i style='mso-bidi-font-style:normal'>et al, <span style='font-weight:normal'>In preparation <span lang=EN-GB>3. Pyne, Noy, Main, Velasco, <span class=SpellE>Mitchenall, <span style='mso-bidi-font-style: italic'>Cugliandolo, <span class=SpellE>Piperakis, Stevenson, Hoogenboom, Bates, Maxwell and Harris, In preparation <span lang=EN-GB>4. Watson, Guilbau, Yoshua, Fogg, Zechiedrich, Leake and Noy, In preparationNon UBCUnreviewedAuthor affiliation: University of YorkResearche