We present parmbsc1, a new force-field for DNA atomistic simulation, which has been parameterized from high-level quantum mechanical data and tested for nearly 100 systems (~140 μs) covering most of the DNA structural space. Parmbsc1 provides high quality results in diverse systems, solving problems of previous force-fields. Parmbsc1 aims to be a reference force-field for the study of DNA in the next decade. Parameters and trajectories are available at http://mmb.irbbarcelona.org/ParmBSC1/.

The dynamics of proteins in aqueous solution has been investigated through a massive approach based on ''state of the art'' molecular dynamics simulations performed for all protein metafolds using the four most popular force fields (OPLS, CHARMM, AMBER, and GROMOS). A detailed analysis of the massive database of trajectories (>1.5 terabytes of data obtained using Ϸ50 years of CPU) allowed us to obtain a robust-consensus picture of protein dynamics in aqueous solution.force field ͉ molecular dynamics ͉ molecular modeling ͉ protein structure

Last generation of force-fields are raising expectations on the quality of molecular dynamics (MD) simulations of DNA, as well as to the belief that theoretical models can substitute experimental ones in several cases. However these claims are based on limited benchmarks, where MD simulations have shown the ability to reproduce already existing ‘experimental models’, which in turn, have an unclear accuracy to represent DNA conformation in solution. In this work we explore the ability of different force-fields to predict the structure of two new B-DNA dodecamers, determined herein by means of 1H nuclear magnetic resonance (NMR). The study allowed us to check directly for experimental NMR observables on duplexes previously not solved, and also to assess the reliability of ‘experimental structures’. We observed that technical details in the annealing procedures can induce non-negligible local changes in the final structures. We also found that while not all theoretical simulations are equally reliable, those obtained using last generation of AMBER force-fields (BSC1 and BSC0OL15) show predictive power in the multi-microsecond timescale and can be safely used to reproduce global structure of DNA duplexes and fine sequence-dependent details.

We present a systematic study of the long-timescale dynamics of the Drew–Dickerson dodecamer (DDD: d(CGCGAATTGCGC)2) a prototypical B-DNA duplex. Using our newly parameterized PARMBSC1 force field, we describe the conformational landscape of DDD in a variety of ionic environments from minimal salt to 2 M Na+Cl− or K+Cl−. The sensitivity of the simulations to the use of different solvent and ion models is analyzed in detail using multi-microsecond simulations. Finally, an extended (10 μs) simulation is used to characterize slow and infrequent conformational changes in DDD, leading to the identification of previously uncharacterized conformational states of this duplex which can explain biologically relevant conformational transitions. With a total of more than 43 μs of unrestrained molecular dynamics simulation, this study is the most extensive investigation of the dynamics of the most prototypical DNA duplex.