Molecular dynamics simulations have been used to compare the structure and
dynamics of three A-tract-containing DNA dodecamer sequences: d(CGCAAATTTGC
G)(2), d(CGCAIATMTGCG)(2), and d(CGCIIIMMMGCG)(2), when M = 5-methylcytosin
e. The simulations shed light on experimental observations regarding DNA be
nding induced by these sequences. We find that replacing an A . T base pair
by an I . M base pair does far more to the structure and particularly dyna
mics of the oligonucleotides than might be expected if the substitution wer
e regarded as just exchanging a hydrogen bond donor and acceptor across the
DNA major groove. The evaluation of the molecular dynamics data is greatly
simplified by the application of the method of principal component analysi
s. This allows key differences in the structures and dynamics of the three
systems to be readily discerned. Three major modes of deformation are obser
ved, the amplitudes and/or average values of which can vary with sequence.
The results allow a simple interpretation of the effects of A . T to I . M
substitutions on DNA bending and point to the importance of DNA flexibility
, as much as static structure, in determining macroscopic behavior.