Helical parameters, fluctuations, alternative hydrogen bonding, and bending in oligonucleotides containing a mistmatched base-pair by NOESY distance restrained and distance free molecular dynamics.

We have analysed and compared the molecular structures and dynamics of the DNA duplex, that corresponds to the sequence 29 to 39 of the K-ras gene, where the central base-pair is the normal C.G base or a mismatch base-pair C.A, C.A+, A.G and A+.G. Molecular dynamics runs of 100 picoseconds without or with distance restraints derived from NOE measurements are analysed and compared in all cases. (1) The EMBO convention of helical parameters for nucleic acids is extended to account for the construction and the description of any DNA mismatched base-pair. (2) Both types of MD runs reproduce very well all NMR data, except the H8 H2 inter-residue distances where agreement is not as good. (3) Average parameter values and fluctuations are in good agreement with results derived from persistence length and torsion modulus measurements. (4) Our molecular dynamics suggest the presence, in certain cases, of three-centred hydrogen bonds, which should be viewed as an equilibrium between hydrogen-bonding alternatives. In the case of the C.A mismatch, we observe the correlation between transient DNA bending and possible hydrogen bonding between a base and its 5' neighbour on the opposite strand in the sequence CCA. (5) These molecular dynamics analyses and observations provide a coherent view for the results obtained from recent DNA crystal structures and for results derived from other techniques such as gel electrophoresis at C.A steps.