Formation and repair of DNA lesions embraces a rich and combinatorial chemistry, where atomic-scale simulations are most helpful to complement and expand experimental evidences. This biopolymer constitutes a critical testcase at the crossroad of several timely methodological developments of GPU-accelerated MD codes, polarizable force fields and multiscale approaches. First, I will show how MD simulations capture also DNA-photosensitizers interactions, which constitute our starting point for triplet-triplet energy transfer, probe new excited-state mechanisms for DNA photostability and rationalize the photochemistry of drugs within DNA owing to QM/MM-MD schemes. I will present our recent efforts to achieve a robust, computationally-driven description of DNA lesions. Intensive molecular dynamics allow to monitor the structural distortion induced by a DNA lesion within an oligonucleotide or within a nucleosome core particle. Capturing the dynamics of damaged DNA, through microsecond-range simulations, palliates the absence of NMR, FRET or X-ray data and delineates rule-of-thumbs for the non-covalent forces that drive sequence recognition and repair. Within the nucleosome, our simulations unambiguously reveal non-covalent interactions between DNA defects and histone tails that were surmised experimentally (see Figure 1). This opens the door for establishing computational cartography of guanine oxidative hot spots in nucleosomal DNA.
After undergraduate studies at the Ecole Normale Superieure de Paris, Elise Dumont obtained her Ph.D. in 2006 at University Paris 6. Since 2008 she has been Professor at the ENS Lyon, starting a new research line in computational biochemistry. Most of her research focuses on DNA damage and repair, and is led in strong collaboration with theoreticians, biochemists and biologists. In 2013 she defended her habilitation, and since 2015 she has started new collaborations with experimentalists in Lyon, giving rise to a new facet of her research lines, related to supramolecular and inorganic chemistry where molecular dynamics simulations are sought to reveal non-covalent interactions at protein-protein interfaces. In 2019, she was nominated as a junior member of the Institut Universitaire de France.
Seminar Series by the NYU-ECNU Center for Computational Chemistry at NYU Shanghai