Exocyclic groups in the minor groove influence the backbone conformation of DNA

Exocyclic groups in the minor groove of DNA modulate the affinity and positioning of nucleic acids to the histone protein. The addition of exocyclic groups decreases the formation of this protein-DNA complex, while their removal increases nucleosome formation. On the other hand, recent theoretical results show a strong correlation between the B-I/B-II phosphate backbone conformation and the hydration of the grooves of the DNA. We performed a simulation of the d(CGCGAATTCGCG)(2) Drew Dickerson dodecamer and one simulation of the d(CGCIAATTCGCG)(2) dodecamer in order to investigate the influence of the exocyclic amino group of guanine. The removal of the amino group introduces a higher intrinsic flexibility to DNA supporting the suggestions that make the enhanced flexibility responsible for the enlarged histone complexation affinity. This effect is attributed to changes in the destacking interactions of both strands of the DNA. The differences in the hydration of the minor groove could be the explanation of this flexibility. The changed hydration of the minor groove also leads to a different B-I/B-II substate pattern. Due to the fact that the histone preferentially builds contacts with the backbone of the DNA, we propose an influence of these B-I/B-II changes on the nucleosome formation process. Thus, we provide an additional explanation for the enhanced affinity to the histone due to removal of exocyclic groups. In terms of B-I/B-II we are also able to explain how minor groove binding ligands could affect the nucleosome assembly without disrupting the structure of DNA.