The DNA double helix is known to exist in many different conformational states, from the compact right-handed A-form to the extended left-handed Z-form. To better understand the variety of double helical forms and the response of DNA to bound protein and drugs, a thorough analysis of known high-resolution crystal structures has been performed using the 3DNA software package (1). We find subtle, sequence-dependent differences in the mean geometry of complementary Watson-Crick base pairs in the A and B helical forms. We are studying the relationship between these structural tendencies and the observed ease of conformational transformation (2). We have also generated an updated set of sequence-dependent empirical energy functions based on 173 DNA-protein crystal complexes corresponding to an almost two fold increase in the number of structures and dimer steps over past analyses (3). We can now distinguish A- and B-like base pair-steps in the protein bound duplex. We are using the many base pair-steps that fall into an intermediate range between the A and B helical form to decipher the likely transitional states.

1. Lu XJ, Shakked Z, Olson WK (2000) J Mol Biol; 300(4):819-40
2. Ivanov VI, Minchenkova LE (1995) Mol Biol; 28(6):780-8
3. Olson WK, Gorin AA, Lu XJ, Hock LM, Zhurkin VB (1998) Proc Natl Acad Sci U S A 95(19):11163-8