Probabilistic Interpretation of NMR J -Couplings Determines BI-BII State Equilibria in DNA.

Interpretation of 3 J P,H3' NMR scalar spin-spin coupling constants in DNA becomes more reliable by including distinct structural states such as BI and BII, using the weighted-static or, better still, the recently implemented adiabatic-MD (Ad-MD) method. The calculation method employs an adiabatic ("Ad") dependence of 3 J P,H3' coupling on NMR-assigned torsion angle, ε, weighted by P (ε) probability distribution calculated by molecular dynamics (MD). Ad-MD calculations enable cross-validation of the bsc1, OL15, and OL21 force fields and various parametrizations of the Karplus equation describing the dependence of 3 J P,H3' coupling on ε torsion (KE). The mean absolute deviation of Ad-MD 3 J P,H3' couplings from the experimental values in Dickerson-Drew DNA is comparable to the scatter of 3 J P,H3' couplings among four separate NMR experiments. A commonly accepted assumption of homogeneity of one kind of structure-dynamic state within DNA (BI or BII) is questionable because the principal characteristics of relevant P (ε) probabilities (shapes and positioning) vary with DNA sequence. The theory outlined in the present work sets limits to future reparameterization of MD force fields, as relevant to NMR data.