Inferring DNA kinkability from biased MD simulations

In several biological processes, such as looping, supercoiling and DNA-protein interactions, DNA is subject to very strong deformations. While coarse-grained models often approximate DNA as a smoothly bendable polymer, experimental and theoretical studies demonstrated that mechanical stress can induce localized kinks. Here, we employ the Rigid Base Biasing of Nucleic Acids (RBB-NA) algorithm to systematically probe the properties of highly deformed DNA in all-atom simulations of a few dodecamers. A simultaneous bias in bending (roll) and twist is applied locally, to two consecutive base-pairs in the center of the dodecamers. Using umbrella sampling we construct free energy landscapes that reveal sequence-dependent effects for kink formation and quantify the energetic cost of kinking. We identify distinct features of the free energies highlighting anharmonic effects, such as asymmetries in the positive vs. negative roll. Our analysis suggests two distinct kinks characterized either by positive roll and undertwisting (twist-bend kinks) or by negative roll without excess twist (pure bend kinks). The former are frequently observed in DNA-protein structures and expected to be favored in-vivo in negatively supercoiled chromosomes. The latter have been observed in DNA simulations of minicircles and are favored in torsionally constrained DNA.