Exploring ion induced folding of a single-stranded DNA oligomer from molecular simulation studies

Abstract

One crucial issue in DNA hydration is the effect of salts on its conformational features. This has relevance in biology as cations present in the cellular environment shield the negative charges on the DNA backbone, thereby reducing the repulsive force between them. By screening the negative charges along the backbone, cations stabilize the folded structure of DNA. To study the effect of the added salt on single-stranded DNA (ss-DNA) conformations, we have performed room temperature molecular dynamics simulations of an aqueous solution containing the ss-DNA dodecamer with the 5'-CGCGAATTCGCG-3' sequence in the presence of 0.2, 0.5, and 0.8 M NaCl. Our calculations reveal that in the presence of the salt, the DNA molecule forms more collapsed coil-like conformations due to the screening of negative charges along the backbone. Additionally, we demonstrated that the formation of an octahedral inner-sphere complex by the strongly bound ion plays an important role in the stabilization of such folded conformation of DNA. Importantly, it is found that ion-DNA interactions can also explain the formation of non-sequential base stackings with longer lifetimes. Such non-sequential base stackings further stabilize the collapsed coil-like folded form of the DNA oligomer.

Autoantibody Profiling in Lupus Patients using Synthetic Nucleic Acids

“…Therefore, we utilized the ED-10 structure to model anti-dsDNA-antibody complexes. Recently, it was reported that aromatic interactions mediate the 5′-base specificity of the ssDNA-binding antibody ED-10 31 . In our model, ED-10 binds to base pairs within double helix, leading to partially unwound dsDNA (Fig.…”

“…Multiple healthy subjects had elevated titers of a-ssDNA, but not of a-dsDNA. This could be caused by coiling of the ss antigen into 3D shapes that may interact non-specifically 31 . Previously it was suggested that elevated a-ssDNA titers is a distinctive feature of drug-induced SLE (DISLE) 32 .…”

Dynamics of physiologically relevant noncanonical DNA structures: an overview from experimental and theoretical studies

“…As shown in Figure 2A, MD simulations on a single strand of the Dickerson-Drew dodecamer showed the molecule undergoing large conformational changes, transforming from an ordered base-stacked form to a globular coil structure, in the nanosecond time scale [43]. Counterions stabilize the globular conformation by neutralizing intra-strand repulsion between phosphate backbones thereby favoring ssDNA folding [44]. The conformational transition is mediated by formation of basestacking interactions between non-consecutive bases (i with i + 2 or i + 3).…”

Effective Repulsion Between Oppositely Charged Particles in Symmetrical Multivalent Salt Solutions: Effect of Salt Valence

“…Salt ions can regulate the effective interactions among polyelectrolytes such as colloids [1][2][3][4][5][6][7], nucleic acids [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22], and proteins [23][24][25][26][27][28][29], and consequently impact diverse physical phenomena including the structural assembly of polyelectrolytes [30], the stability of colloids [31,32], and the collapse of nucleic acids [33][34][35]. Generally, a polyelectrolyte solution is often modeled through the Poisson-Boltzmann (PB) equation since the equation has a simple form and is rather successful in predicting the properties of polyelectrolytes in aqueous and monovalent salt solutions [36,37].…”