Although DNA bending plays a crucial role in several biological processes, very little is known experimentally about the relationship between sugar phosphate conformation and sequence directed bending. We have used 21) NMR experiments to determine both proton-proton and proton-phosphorus coupling constants, which define the sugar phosphate backbone geometry in the I 1-mer A-tract DNA duplex C-C-T-C-A-A-A-C-T-C-C G-G-A-G-T-T-T-G-A-G-G Along each chain of the duplex, we have determined the sugar pucker, 'torsional preferences and conformational averaging about the CY-03% C4'-C5' and CN-05' bonds for each nucleotide. We have been able to define the sequence dependent correlated backbone conformational changes and the propagation of local distortions at the backbone upon DNA bending. While the A-tract itself is in B-form., it displays local polymorphism in that the C4'-C5' torsion of the T-strand becomes increasingly trans towards the 5' end of the A-tract and the minor groove narrows towards the 3' end. In fact, at the 5' end of the A-tract in one of the strands, at the thymine-purine junction, we detect significant populations of noncanonical B-DNA trans conformation at the C4'-C5' exocyclic bond. This can increase the interphosphate distance and lead to local unwinding of the duplex and rolling of the base pair into the major groove, and thereby create a kink or hinge. At the Y-end of the Atract in the purine-thymin e step, the duplex is compressed by the presence of a junction between A and B forms of DNA exclusively in one strand, with consequent reduction of the phosphatephosphate distance. Structural distortions are extremely localized with little or no propagation. It is likely that transcription factor proteins recognize these preexisting deformations in the free DNA itself and mold it into the matrix of the protein. Efforts are underway to combine NOESY and the coupling constant data to derive an equilibrium clusters of conformation via multimodal restrained molecular dynamics.
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