Parmbsc1, a new force field for DNA simulations, was broadly tested on nearly 100 DNA systems and overcame simulation artifacts that affected previous force fields. We present parmbsc1, a force field for DNA atomistic simulation, which has been parameterized from high-level quantum mechanical data and tested for nearly 100 systems (representing a total simulation time of ∼140 μs) covering most of DNA structural space. Parmbsc1 provides high-quality results in diverse systems. Parameters and trajectories are available at http://mmb.irbbarcelona.org/ParmBSC1/ .

It is well recognized that base sequence exerts a significant influence on the properties of DNA and plays a significant role in protein–DNA interactions vital for cellular processes. Understanding and predicting base sequence effects requires an extensive structural and dynamic dataset which is currently unavailable from experiment. A consortium of laboratories was consequently formed to obtain this information using molecular simulations. This article describes results providing information not only on all 10 unique base pair steps, but also on all possible nearest-neighbor effects on these steps. These results are derived from simulations of 50–100 ns on 39 different DNA oligomers in explicit solvent and using a physiological salt concentration. We demonstrate that the simulations are converged in terms of helical and backbone parameters. The results show that nearest-neighbor effects on base pair steps are very significant, implying that dinucleotide models are insufficient for predicting sequence-dependent behavior. Flanking base sequences can notably lead to base pair step parameters in dynamic equilibrium between two conformational sub-states. Although this study only provides limited data on next-nearest-neighbor effects, we suggest that such effects should be analyzed before attempting to predict the sequence-dependent behavior of DNA.

We present the first microsecond MD simulation of B-DNA. Trajectory shows good agreement with available data and clarifies the μs dynamics of DNA. The duplex is sampling the B-conformation, but many relevant local transitions are found, including S → N repuckers (up to 7 N-sugars are found simultaneously), local B_II transitions (15% of the dinucleotides are in B_II-form; some of these forms are stable for up to 7 ns), and sequence-dependent α/γ transitions (happening in the 7−50 ns time scale, and being stable for up to 80 ns). Partial and total openings are often detected, but no base flipping is found. A·T openings happen after amplification of propeller twist movements, while G·C pairs (which can be opened for up to 1 ns) are opened by a complex mechanism which is often catalyzed by cations. A high affinity Na⁺ binding site is found in the center of the minor groove. Access to this site by cations is difficult (average entry time 400 ns), but once inside, the ion remains for long periods of time (10−15 ns), producing a sizable narrowing of the minor groove. The essential dynamics of DNA fits well with the pattern of deformation needed to (i) sample uncommon right-handed forms and (ii) sample conformations adopted by DNA when bound to proteins. Clearly, DNA has evolved to be not only a stable structure able to maintain and transmit the genetic information but also a flexible entity whose intrinsic pattern of deformability matches its functional needs.

We present the results of microsecond molecular dynamics simulations carried out by the ABC group of laboratories on a set of B-DNA oligomers containing the 136 distinct tetranucleotide base sequences. We demonstrate that the resulting trajectories have extensively sampled the conformational space accessible to B-DNA at room temperature. We confirm that base sequence effects depend strongly not only on the specific base pair step, but also on the specific base pairs that flank each step. Beyond sequence effects on average helical parameters and conformational fluctuations, we also identify tetranucleotide sequences that oscillate between several distinct conformational substates. By analyzing the conformation of the phosphodiester backbones, it is possible to understand for which sequences these substates will arise, and what impact they will have on specific helical parameters.