B-I reversible arrow B-II substate transitions induce changes in the hydration of B-DNA, potentially mediating signal transduction from the minor to major groove

The EcoRI DNA dodecamer d(CGCGAATTCGCG)(2) was investigated by a 10 ns mole cular dynamics simulation. The B-II substate distribution within one strand is shown to give an alternating pattern and thus avoids two successive pho sphates remaining simultaneously in the B-II substate. Increased B-II popul ation (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 C heatham et al. [Cheatham, T. E., III; Cieplak, P.; Kollman, P. A. J. Biomol . Struct. Dyn. 1999, 16, 845-862]. Furthermore, B, reversible arrow B-II co nformational transitions are shown to correlate with the hydration pattern of the phosphate group, the sugar oxygen, and the minor and the major groov e. 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.