BI ⇌ BII Substate Transitions Induce Changes in the Hydration of B-DNA, Potentially Mediating Signal Transduction from the Minor to Major Groove

The Eco RI DNA dodecamer d(CGCGAATTCGCG) 2 was investigated by a 10 ns molecular dynamics simulation. The B II substate distribution within one strand is shown to give an alternating pattern and thus avoids two successive phosphates remaining simultaneously in the B II substate. Increased B II population (B I /B II ratio of 3.7 compared to 9.2 in a previous simulation) was observed by employing improved force field parameters derived recently by Cheatham et al. [Cheatham, T. E., III; Cieplak, P.; Kollman, P. A. J. Biomol. Struct. Dyn. 1999, 16, 845−862]. Furthermore, B I ⇌ B II conformational transitions are shown to correlate with the hydration pattern of the phosphate group, the sugar oxygen, and the minor and the major groove. Therefore, B I /B II substates can act as an additional conversation tool to transfer binding information from a drug ligand in the minor groove to a protein binding site in the major groove.