| Abstract
| - Molecular dynamics (MD) simulations were conducted for a G−T mismatch-containing DNAdecamer, d(CCATGCGTGG)2, and its Watson−Crick parent sequence, d(CCACGCGTGG)2. Dynamics inunrestrained MD trajectories were in poor agreement with prior 13C NMR studies. However, the accuracyof the trajectories was improved by the use of time-averaged interatomic distance restraints derived from1H NMR. Postprocess smoothing of the trajectories further improved accuracy. Comparison of restrainedand smoothed trajectories of the two DNA molecules revealed distinct differences in dynamics. The majorgroove width of the mismatched oligomer was more variable over the course of the simulation comparedto its parent sequence. Greater variability in helical parameters stretch and opening for the mismatchesindicated less kinetically stable base pairing. Interbase helical parameters rise, roll, and tilt were also morevariable in certain base steps involving mismatched bases. These dynamic differences between normaland G−T mismatched DNA reflect differences in local flexibility that may play a role in mismatch recognitionby the MutS. A potential alternate G−T mismatch binding mode for MutS is also proposed.
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