title: Small local variations in B-form DNA lead to a large variety of global geometries which can accommodate most DNA-binding protein motifs.
abstract: BACKGROUND
  An important question of biological relevance is the polymorphism of the double-helical DNA structure in its free form, and the changes that it undergoes upon protein-binding. We have analysed a database of free DNA crystal structures to assess the inherent variability of the free DNA structure and have compared it with a database of protein-bound DNA crystal structures to ascertain the protein-induced variations.
  
  
  RESULTS
  Most of the dinucleotide steps in free DNA display high flexibility, assuming different conformations in a sequence-dependent fashion. With the exception of the AA/TT and GA/TC steps, which are 'A-phobic', and the GG/CC step, which is 'A-philic', the dinucleotide steps show no preference for A or B forms of DNA. Protein-bound DNA adopts the B-conformation most often. However, in certain cases, protein-binding causes the DNA backbone to take up energetically unfavourable conformations. At the gross structural level, several protein-bound DNA duplexes are observed to assume a curved conformation in the absence of any large distortions, indicating that a series of normal structural parameters at the dinucleotide and trinucleotide level, similar to the ones in free B-DNA, can give rise to curvature at the overall level.
  
  
  CONCLUSIONS
  The results illustrate that the free DNA molecule, even in the crystalline state, samples a large amount of conformational space, encompassing both the A and the B-forms, in the absence of any large ligands. A-form as well as some non-A, non-B, distorted geometries are observed for a small number of dinucleotide steps in DNA structures bound to the proteins belonging to a few specific families. However, for most of the bound DNA structures, across a wide variety of protein families, the average step parameters for various dinucleotide sequences as well as backbone torsion angles are observed to be quite close to the free 'B-like' DNA oligomer values, highlighting the flexibility and biological significance of this structural form.
authors.affiliation: Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India. arvind@mbu.iisc.ernet.in
authors.forename: Arvind
authors.initials: A
authors.lastname: Marathe
authors.forename: Deepti
authors.initials: D
authors.lastname: Karandur
authors.forename: Manju
authors.initials: M
authors.lastname: Bansal
mesh_terms: D020816:Amino Acid Motifs; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D044704:DNA, A-Form / Q000737:chemistry / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D018900:Dinucleotide Repeats; D009690:Nucleic Acid Conformation
chemical_list: D044704:DNA, A-Form; D004268:DNA-Binding Proteins; D004247:DNA