Role of protein interactions in stabilizing canonical DNA features in simulations of DNA in crowded environments

BACKGROUND: Cellular environments are highly crowded with biological macromolecules resulting in frequent non-specific interactions. While the effect of such crowding on protein structure and dynamics has been studied extensively, very little is known how cellular crowding affects the conformational sampling of nucleic acids. RESULTS: The effect of protein crowding on the conformational preferences of DNA (deoxyribonucleic acid) is described from fully atomistic molecular dynamics simulations of systems containing a DNA dodecamer surrounded by protein crowders. From the simulations, it was found that DNA structures prefer to stay in B-like conformations in the presence of the crowders. The preference for B-like conformations results from non-specific interactions of crowder proteins with the DNA sugar-phosphate backbone. Moreover, the simulations suggest that the crowder interactions narrow the conformational sampling to canonical regions of the conformational space. CONCLUSIONS: The overall conclusion is that crowding effects may stabilize the canonical features of DNA that are most important for biological function. The results are complementary to a previous study of DNA in reduced dielectric environments where reduced dielectric environments alone led to a conformational shift towards A-DNA. Such a shift was not observed here suggested that the reduced dielectric response of cellular environments is counteracted by non-specific interactions with protein crowders under in vivo conditions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13628-018-0048-y) contains supplementary material, which is available to authorized users.