An in-depth look at DNA crystals through the prism of molecular dynamics simulations

ABSTRACT X-ray crystallography has been traditionally considered as the primary tool for the determination of biomolecular structures and its derived models are taken as the gold standard in structural biology. However, contacts formed through the crystal lattice are known to affect the structures, especially in the case of small and flexible molecules, like DNA oligos, introducing drastic changes in the structure with respect to the solution phase. Furthermore, it is still unknown why molecules crystallize in certain symmetry groups and how the associated lattice impacts their structure. The role of crystallization additives and whether they are just innocuous and unspecific catalyzers of the crystallization process also remains unclear. On account of a massive computational effort and the use of the latest generation force field, we were able to describe with unprecedented level of detail the nature of intermolecular forces that participate in the stabilization of B-DNA crystals in various symmetry groups and in different solvent environments. We showed that the stability of the crystal lattice and the type of crystallization additives are tightly coupled, and certain symmetry groups are only stable in the presence of a specific crystallization additive (i.e., spermine). Additives and crystal contacts induce small but non-negligible changes in the physical properties of DNA.