Systematic Comparison of Atomistic Force Fields for the Mechanical Properties of Double-Stranded DNA

• Published in: Journal of chemical theory and computation 2024-03, Vol.20 (5), p.2261-2272
• Main Authors: Roldán-Piñero, Carlos, Luengo-Márquez, Juan, Assenza, Salvatore, Pérez, Rubén
• Format: Article
• Language: English
• Subjects: Biomolecular Systems; Mechanical analysis; Mechanical properties; Molecular dynamics; Parameters
• ISSN: 1549-9618; 1549-9626
• DOI: 10.1021/acs.jctc.3c01089

The response of double-stranded DNA to external mechanical stress plays a central role in its interactions with the protein machinery in the cell. Modern atomistic force fields have been shown to provide highly accurate predictions for the fine structural features of the duplex. In contrast, and despite their pivotal function, less attention has been devoted to the accuracy of the prediction of the elastic parameters. Several reports have addressed the flexibility of double-stranded DNA via all-atom molecular dynamics, yet the collected information is insufficient to have a clear understanding of the relative performance of the various force fields. In this work, we fill this gap by performing a systematic study in which several systems, characterized by different sequence contexts, are simulated with the most popular force fields within the AMBER family, bcs1 and OL15, as well as with CHARMM36. Analysis of our results, together with their comparison with previous work focused on bsc0, allows us to unveil the differences in the predicted rigidity between the newest force fields and suggests a roadmap to test their performance against experiments. In the case of the stretch modulus, we reconcile these differences, showing that a single mapping between sequence-dependent conformation and elasticity via the crookedness parameter captures simultaneously the results of all force fields, supporting the key role of crookedness in the mechanical response of double-stranded DNA.