Understanding the Origin of Structural Diversity of DNA Double Helix

Valeri Poltev,Eduardo Gonzalez,Victor M Anisimov,Alexandra Deriabina,Dolores Garcia,Francisco Rivas,Andrea Ruiz,Veronica Dominguez

doi:10.3390/computation9090098

Valeri Poltev, Eduardo Gonzalez + Show 6 more

Open Access

https://doi.org/10.3390/computation9090098

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Abstract

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.

Highlights

The DNA duplex, which is known as the main molecule of life, is a complex of two antiparallel complementary copolymers of four nucleotide units
Based on limited data on optimized BI conformations of deoxydinucleoside monophosphates (dDMPs) [6], we suggested that the uniform sugar-phosphate backbone plays a substantial role in the nucleotide sequence-dependence of the 3D structure of the Watson–Crick duplexes (WCDs)
We extend our computations and analysis to conformational parameters of dDMPs corresponding to NtCs compatible with the formation of a double helix with Watson–Crick nucleoside pairs, i.e., with A:T and G:C complementary base pairs and an anti-orientation of base and deoxyribose in both nucleosides

Summary

Introduction

The DNA duplex, which is known as the main molecule of life, is a complex of two antiparallel complementary copolymers of four nucleotide units. We extend our computations and analysis to conformational parameters of dDMPs corresponding to NtCs compatible with the formation of a double helix with Watson–Crick nucleoside pairs, i.e., with A:T and G:C complementary base pairs and an anti-orientation of base and deoxyribose in both nucleosides These “non-canonical” (non-BI and non-AI) conformations of minimal fragments of DNA chains arise as a result of existence of various sets of regions of SPB torsions that satisfy Watson–Crick nucleoside pairing in the right-handed fragment of the double helix structure. For some of the NtC classes, the optimized geometries of dDMP or cdDMP do not structurally match the corresponding fragments of the longer duplex

Materials and Methods

Selection of Conformational Classes of DNA Minimal Fragments

Method