Understanding the Origin of Structural Diversity of DNA Double Helix

• Main Authors: Valeri Poltev, Victor M. Anisimov, Veronica Dominguez, Andrea Ruiz, Alexandra Deriabina, Eduardo Gonzalez, Dolores Garcia, Francisco Rivas
• Format: Article
• Language: English
• Published: MDPI AG 2021-09-01
• Series: Computation
• Subjects: DNA conformations; sequence dependence; density functional theory; ab initio computations; molecular mechanics; deoxydinucleoside monophospates
• Online Access: https://www.mdpi.com/2079-3197/9/9/98

Deciphering the contribution of DNA subunits to the variability of its 3D structure represents an important step toward the elucidation of DNA functions at the atomic level. In the pursuit of that goal, our previous studies revealed that the essential conformational characteristics of the most populated “canonic” BI and AI conformational families of Watson–Crick duplexes, including the sequence dependence of their 3D structure, preexist in the local energy minima of the elemental single-chain fragments, deoxydinucleoside monophosphates (dDMPs). Those computations have uncovered important sequence-dependent regularity in the superposition of neighbor bases. The present work expands our studies to new minimal fragments of DNA with Watson–Crick nucleoside pairs that differ from canonic families in the torsion angles of the sugar-phosphate backbone (SPB). To address this objective, computations have been performed on dDMPs, cdDMPs (complementary dDMPs), and minimal fragments of SPBs of respective systems by using methods of molecular and quantum mechanics. These computations reveal that the conformations of dDMPs and cdDMPs having torsion angles of SPB corresponding to the local energy minima of separate minimal units of SPB exhibit sequence-dependent characteristics representative of canonic families. In contrast, conformations of dDMP and cdDMP with SPB torsions being far from the local minima of separate SPB units exhibit more complex sequence dependence.