Exploring potentially alternative non-canonical DNA duplex structures through simulation |
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| Authors: | Rodrigo Galindo-Murillo Thomas E Cheatham III Robert C Hopkins |
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| Institution: | 1. Department of Medicinal Chemistry, L. S. Skaggs Pharmacy Institute, University of Utah, Salt Lake City, UT, USA;2. Department of Chemistry, University of Houston—Clear Lake, Houston, TX, USACommunicated by Ramaswamy H. Sarma;3. Department of Medicinal Chemistry, L. S. Skaggs Pharmacy Institute, University of Utah, Salt Lake City, UT, USA |
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| 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 |
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| Keywords: | configuration II DNA double-stranded DNA AMBER interstrand binding energy left-handed DNA molecular dynamics MM-PBSA |
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