Anna Panchenko

Queen’s University, Kingston, Ontario, Canada

Key Challenges in Modeling Protein–DNA Interactions in Chromatin

Abstract The key challenges in modeling of protein–DNA interactions in chromatin arise from its multiscale, dynamic, and heterogeneous nature, the coupling between DNA sequence-dependent mechanics and nucleosome organization, and the cooperativity among many DNA binding factors. Such a complex nature of protein–DNA interactions in chromatin makes them difficult to study using experimental approaches alone. Therefore, we develop integrative approaches that combine atomistic molecular dynamics simulations and molecular modeling with various experimental methods, such as Cryo-ET, NMR spectroscopy, MNase-seq, and binding assays. Our findings show how DNA modifications and protein missense mutations can impact protein-DNA binding and chromatin dynamics.