Alladi Ramakrishnan Hall

Selective Regulation of Nucleic Acid Complexes from a Molecular Dynamics Simulation Perspective

Mithun Biswas

University of Freiburg, Germany

Understanding the effect of subtle modifications in structure on the stability of nucleic acid complexes is the key to regulate gene access and to achieve a desired function in nanotechnological applications. Here I present two examples of functional regulation of a nucleic acid complex via commonly used methods, namely, point-mutation of amino acids and attachment of a photoswitchable group and shed light on regulatory mechanisms by employing all-atom molecular dynamics simulations. In the first example I provide a detailed overview of the structural changes in nucleosome, the building block of eukaryotic chromatin, upon modifications of histone tails, which are disorderd domains protruding out of the nucleosome and primary sites of post-translational modifications in histones. The study revealed that on truncation of H4 or H2B tails no structural change occurs in histones. However, H3 or H2A tail truncation results in structural alterations in the histone core domain, and in both the cases the structural change occurs in the H2Aα3 domain. It also showed a crucial role of the H2A C terminal tail in regulating nucleosome stability. The correlation between tail-truncation and structural changes revealed in this study sheds light on allosteric regulation of nucleosome stability. In the second part, I explore the molecular basis of the photoinduced conformational changes in nucleic acids by covalent attachment of azobenzene, a paradigm example that has been investigated in many recent experiments. In DNA, attachment of azobenzene leads to a distortion of the DNA helical conformation which is similar for the *trans* and *cis* forms. However, the *trans* form is stabilized by favorable stacking interactions while the *cis* form is found to remain flipped out of the base pair stacked position. The distorted DNA retains native-like pairing of bases at ambient temperatures but shows weaker base paring compared to native DNA at an elevated temperature.