Exploring potentially alternative non-canonical DNA duplex structures through simulation

Abstract

Hopkins proposed an alternative and chirally distinct family of double-stranded DNA (dsDNA) models that have antiparallel chains with 5′→3′ senses opposite to those of the right-handed Watson–Crick (WC) family. Termed configuration II, this family of dsDNA models contains both right-handed (II-R) and left-handed (II-L) forms, with Z-DNA as an example of the latter. Relative interstrand binding energies for six DNA duplex models, two each of configuration I-R (standard WC canonical B-DNA), II-R, and II-L for the duplex d(CGCGAATTCGCG), have been estimated under identical conditions using MM-PBSA analysis from molecular dynamics trajectories using three different AMBER force fields. These simulations support the stereo chemical soundness of configuration II dsDNA forms. Recent force fields (Barcelona Supercomputing Center [BSC] [bsc1] and Olomouc 2015 [OL15]) successfully render stable II-L structures, whereas the previous force field, bsc0, generated stable II-R structures, although with an energy difference between II-R and II-L of ∼30 kcal/mol.

Communicated by Ramaswamy H. Sarma

Keywords:

• configuration II DNA
• double-stranded DNA
• AMBER
• interstrand binding energy
• left-handed DNA
• molecular dynamics
• MM-PBSA

Acknowledgements

Prof. Hopkins passed away unexpectedly before this article was finished and properly published. He originally approached our research team in 2011 with his models and an early draft of this article based on molecular mechanics analysis of those models; we extended his work with large scale biomolecular simulation and analysis. We have made our best effort to extend and complete his original ideas. We dedicate this work to his memory.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research was enabled by the Blue Waters sustained-petascale computing project (NSF OCI 07-25070 and PRAC OCI-1036208), the NSF Extreme Science and Engineering Discovery Environment (XSEDE, OCI-1053575) and allocation MCA01S027P, and the Center for High Performance Computing at the University of Utah. This work was supported by departmental grants to Professor Hopkins from The Robert A. Welch Foundation (G400042).