A Nanosecond Molecular Dynamics Trajectory for a B DNA Double Helix: Evidence for Substates

Abstract

We report here the results of the three molecular dynamics (MD) simulations on the d(CGCGAATTCGCG) duplex, two for 500 ps and one extended to 1 ns, as a response to serious questions about the sensitivity of the results to trajectory length and choice of starting structure. In 1992 we reported a 140-ps MD on the d(CGCGAATTCGCG) duplex including water and counterions. This simulation utilized the GROMOS force field,2 and irreversible base pair opening events were observed, as with other force field^.^.^ A second simulation employed a harmonic restraint function with GROMOS to assure that Watson-Crick base pairing was maintained intact. The results in the latter case were found to be consistent with available experimental data in comparison both with crystal structure datal and with 2D-NOESY buildup curves obtained from NMR spectro~copy.~~~ Subsequent studies of hydrogen bond interaction energies in Watson-Crick base pairs revealed that GROMOS underestimates these interactions. When a hydrogen bond potential7 was added, the energies compared closely with corresponding experimental data and ab initio quantum mechanical calculations.* The simulations described herein are based on GROMOS with this modification. The current studies also utilize a longer range switching function, which feathers the truncation of potentials over the length scale from 7.5 to 11.5 A and eliminates the tendency of charged groups to cluster at the cutoff limit when potentials are truncated too abr~ptly.~ We treat the effect of counterions implicity, using a reduced charge of -0.24 eu on the phosphate groups.IO All current simulations are carried out using free MD on the dodecamer duplex surrounded by - 3500 water molecules in a hexagonal prism elementary cell of constant volume, treated under periodic boundary conditions to model dilute aqueous (1) Swaminathan, S.; Ravishanker, G.; Beveridge, D. L. J. Am. Chem. Soc. 1991, 113,5027.