Accurate Sequence-Dependent Coarse-Grained Model for Conformational and Elastic Properties of Double-Stranded DNA

S Assenza and R Perez, JOURNAL OF CHEMICAL THEORY AND COMPUTATION, 18, 3239-3256 (2022).

DOI: 10.1021/acs.jctc.2c00138

We introduce MADna, a sequence-dependent coarse-grained model of double- stranded DNA (dsDNA), whereeach nucleotide is described by three beads localized at the sugar, atthe base moiety, and at the phosphate group, respectively. Thesequence dependence is included by considering a step- dependentparametrization of the bonded interactions, which are tuned inorder to reproduce the values of key observables obtained fromexhaustive atomistic simulations from the literature. Thepredictions of the model are benchmarked against an independentset of all-atom simulations, showing that it captures with highfidelity the sequence dependence of conformational and elasticfeatures beyond the single step considered in its formulation. Aremarkably good agreement with experiments is found for both sequence-averaged and sequence-dependent conformational andelastic features, including the stretching and torsion moduli, the twist-stretch and twist-bend couplings, the persistence length, andthe helical pitch. Overall, for the inspected quantities, the model has a precision comparable to atomistic simulations, henceproviding a reliable coarse-grained description for the rationalization of single-molecule experiments and the study of cellularprocesses involving dsDNA. Owing to the simplicity of its formulation, MADna can be straightforwardly included in commonsimulation engines. Particularly, an implementation of the model in LAMMPS is made available on an online repository to ease itsusage within the DNA research community

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