scholarly journals C3′ Stereocentre of Furanose Determines the Helicity of Double-Stranded Nucleic Acids: Towards Etiology of Nucleic Acids

2020 ◽  
Author(s):  
Anuj Kumar ◽  
Amol Tagad ◽  
G. Naresh Patwari
Keyword(s):  
Molecular Dynamics ◽  
Nucleic Acids ◽  
Structural Transition ◽  
Double Helix ◽  
Helical Structure ◽  
Structural Features ◽  
Toggle Switch ◽  
Helix Structure ◽  
Double Helix Structure ◽  
Dynamics Simulations

ABSTRACTRibose containing double-stranded nucleic acids exhibit helical structure, whereas sugar modified (xeno) nucleic acids may exhibit different structural features. The structural landscape of four stereo variants of furanosal nucleic acids and their C2′ deoxy counterparts, explored with molecular dynamics simulations, suggest that the configuration at the C3′ position plays a pivotal role in determining the helicity. The C3′ stereocentre acts as toggle-switch for the helix to ladder structural transformation by changing the nature of intra-strand interactions resulting in the optimal helices for ribose containing double-stranded nucleic acids. Interestingly, lack of chirality at the C2′ position results in better quality helices than inversion of stereochemistry relative to ribose. The etiology of furanosal-RNA over other furanoses can be hypothesized based on the helical structure, which can effectively be exploited by the biological machinery.SIGNIFICANCEThe double helix structure of furanosal RNA is governed by the configuration at the C3′ position. Furanose sugars such as xylose and lyxose where in the configuration at the C3′ position is inverted relative to the ribose do not form double helix structure, instead result in ladder-like structure. The configuration at the C3′ position acts as a toggle switch for the helix to ladder structural transition. Among four furanose sugars viz., ribose, arabinose, xylose, and lyxose, the double-stranded nucleic acids incorporating ribose form helices with best aspect ratio between major and minor grooves.

scholarly journals Adsorption of Chiral [5]-Aza[5]helicenes on DNA Can Modify Its Hydrophilicity and Affect Its Chiral Architecture: A Molecular Dynamics Study

Materials ◽  
2020 ◽  
Vol 13 (21) ◽  
pp. 5031
Author(s):  
Giuseppina Raffaini ◽  
Andrea Mele ◽  
Tullio Caronna
Keyword(s):  
Molecular Dynamics ◽  
Competitive Adsorption ◽  
Double Helix ◽  
Helical Structure ◽  
High Concentration ◽  
Racemic Mixtures ◽  
Preferential Binding ◽  
Biological Environment ◽  
Dynamics Simulations ◽  
Self Aggregation

Helicenes are interesting chiral molecules without asymmetric carbon atoms but with intrinsic chirality. Functionalized 5-Aza[5]helicenes can form non-covalent complexes with anticancer drugs and therefore be potential carriers. The paper highlights the different structural selectivity for DNA binding for two enantiopure compounds and the influence of concentration on their adsorption and self-aggregation process. In this theoretical study based on atomistic molecular dynamics simulations the interaction between (M)- and (P)-5-Aza[5]helicenes with double helix B-DNA is investigated. At first the interaction of single pure enantiomer with DNA is studied, in order to find the preferred site of interaction at the major or minor groove. Afterwards, the interaction of the enantiomers at different concentrations was investigated considering both competitive adsorption on DNA and possible helicenes self-aggregation. Therefore, racemic mixtures were studied. The helicenes studied are able to bind DNA modulating or locally modifying its hydrophilic surface into hydrophobic after adsorption of the first helicene layer partially covering the negative charge of DNA at high concentration. The (P)-enantiomer shows a preferential binding affinity of DNA helical structure even during competitive adsorption in the racemic mixtures. These DNA/helicenes non-covalent complexes exhibit a more hydrophobic exposed surface and after self-aggregation a partially hidden DNA chiral architecture to the biological environment.

Cluster, Surface and Bulk Properties of ZnCd Binary Alloys: Molecular-Dynamics Simulations

2005 ◽  
Vol 502 ◽  
pp. 51-56 ◽  
Author(s):  
Sakir Erkoc
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Density Functional ◽  
Structural Features ◽  
Bulk Materials ◽  
Bulk Properties ◽  
Atom Clusters ◽  
Dynamics Simulations ◽  
Mixed Clusters ◽  
Stable Structures

The structural and electronic properties of isolated neutral ZnmCdn clusters for m+n £ 3 have been investigated by performing density functional theory calculations at B3LYP level. The optimum geometries, vibrational frequencies, electronic structures, and the possible dissosiation channels of the clusters considered have been obtained. An empirical many-body potential energy function (PEF), which comprices two- and three-body atomic interactions, has been developed to investigate the structural features and energetics of ZnmCdn (m+n=3,4) microclusters. The most stable structures were found to be triangular for the three-atom clusters and tetrahedral for the four-atom clusters. On the other hand, the structural features and energetics of Znn-mCdm (n=7,8) microclusters, and Zn50, Cd50, Zn25Cd25, Zn12Cd38, and Zn38Cd12 nanoparticles have been investigated by performing molecular-dynamics computer simulations using the developed PEF. The most stable structures were found to be compact and three-dimensional for all elemental and mixed clusters. An interesting structural feature of the mixed clusters is that Zn and Cd atoms do not mix in mixed clusters, they come together almost without mixing. Surface and bulk properties of Zn, Cd, and ZnCd systems have been investigated too by performing molecular-dynamics simulations using the developed PEF. Surface reconstruction and multilayer relaxation on clean surfaces, adatom on surface, substitutional atom on surface and bulk materials, and vacancy on surface and bulk materials have been studied extensively.

Light Scattering and Flow Dichroism Studies on DNA After the Photoreaction with Psoralen

1972 ◽  
Vol 27 (2) ◽  
pp. 196-200 ◽  
Author(s):  
S. Marciani ◽  
M. Terbojevic ◽  
F. Dall’Acqua
Keyword(s):  
Heat Treatment ◽  
Molecular Weight ◽  
Light Scattering ◽  
Double Helix ◽  
Heat Denaturation ◽  
Scattering Measurements ◽  
Helix Structure ◽  
Double Helix Structure

Light scattering measurements performed on DNA after irradiation in the presence of psoralen clearly show that inter strand cross linkings are present in the macromolecule. In fact after heat denaturation and successive cooling irradiated macromolecule shows a molecular weight practically unchanged while a DNA sample after the same treatment shows a molecular weight half of the intact native DNA. Also the general conformation of irradiated DNA undergoes practically to no modifications after the same heat treatment while native DNA shows itself to have been strongly modified. Moreover, on the basis of flow dichroism determinations, DNA cross-linked by psoralen after heat denaturation showed to be able to restore its ordered double helix structure, during the successive cooling.

scholarly journals Positively and Negatively Hydrated Counterions in Molecular Dynamics Simulations of DNA Double Helix

2020 ◽  
Vol 65 (6) ◽  
pp. 510
Author(s):  
S. Perepelytsya
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Double Helix ◽  
Dipole Moments ◽  
Hydration Shell ◽  
Minor Groove ◽  
Water Molecules ◽  
Negative Hydration ◽  
Dynamics Simulations ◽  
Dna Double Helix

The DNA double helix is a polyanionic macromolecule that is neutralized in water solutions by metal ions (counterions). The property of counterions to stabilize the water network (positive hydration) or to make it friable (negative hydration) is important in terms of the physical mechanisms of stabilization of the DNA double helix. In the present research, the effects of positive hydration of Na+ counterions and negative hydration of K+ and Cs+ counterions incorporated into the hydration shell of the DNA double helix have been studied using molecular dynamics simulations. The results have shown that the dynamics of the hydration shell of counterions depends on the region of the double helix: minor groove, major groove, and outside the macromolecule. The longest average residence time has been observed for water molecules contacting with the counterions localized in the minor groove of the double helix (about 50 ps for Na+ and lower than 10 ps for K+ and Cs+). The estimated potentials of the mean force for the hydration shells of counterions show that the water molecules are constrained too strongly, and the effect of negative hydration for K+ and Cs+ counterions has not been observed in the simulations. The analysis has shown that the effects of counterion hydration can be described more accurately with water models having lower dipole moments.

scholarly journals Multimodal tubulin binding by the yeast kinesin-8, Kip3, underlies its motility and depolymerization

2021 ◽  
Author(s):  
Hugo Arellano-Santoyo ◽  
Rogelio A Hernandez-Lopez ◽  
Emma Stokasimov ◽  
Ray YR Wang ◽  
David Pellman ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Single Molecule ◽  
Conformational Changes ◽  
Intracellular Transport ◽  
Structural Features ◽  
Cellular Processes ◽  
Tubulin Binding ◽  
Dynamics Simulations ◽  
Spatiotemporal Control ◽  
Unique Ability

The microtubule (MT) cytoskeleton is central to cellular processes including axonal growth, intracellular transport, and cell division, all of which rely on precise spatiotemporal control of MT organization. Kinesin-8s play a key role in regulating MT length by combining highly processive directional motility with MT-end disassembly. However, how kinesin-8 switches between these two apparently opposing activities remains unclear. Here, we define the structural features underlying this molecular switch through cryo-EM analysis of the yeast kinesin-8, Kip3 bound to MTs, and molecular dynamics simulations to approximate the complex of Kip3 with the curved tubulin state found at the MT plus-end. By integrating biochemical and single-molecule biophysical assays, we identified specific intra- and intermolecular interactions that modulate processive motility and MT disassembly. Our findings suggest that Kip3 undergoes conformational changes in response to tubulin curvature that underlie its unique ability to interact differently with the MT lattice than with the MT-end.

scholarly journals Mechanistic and Structural Insights on the IL-15 System through Molecular Dynamics Simulations

Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3261
Author(s):  
Sousa ◽  
Laurent ◽  
Quéméner ◽  
Mortier ◽  
Questel
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Structural Features ◽  
Cellular Functions ◽  
Α Subunit ◽  
X Ray Crystallography ◽  
Receptor Complexes ◽  
Protein Interfaces ◽  
Dynamics Simulations ◽  
Comparison Of The Results

Interleukin 15 (IL-15), a four-helix bundle cytokine, is involved in a plethora of different cellular functions and, particularly, plays a key role in the development and activation of immune responses. IL-15 forms receptor complexes by binding with IL-2Rβ- and common γ(γc)-signaling subunits, which are shared with other members of the cytokines family (IL-2 for IL-2Rβ- and all other γc- cytokines for γc). The specificity of IL-15 is brought by the non-signaling α-subunit, IL-15Rα. Here we present the results of molecular dynamics simulations carried out on four relevant forms of IL-15: its monomer, IL-15 interacting individually with IL-15Rα (IL-15/IL-15Rα), with IL-2Rβ/γc subunits (IL-15/IL-2Rβ/γc) or with its three receptors simultaneously (IL-15/IL-15Rα/IL-2Rβ/γc). Through the analyses of the various trajectories, new insights on the structural features of the interfaces are highlighted, according to the considered form. The comparison of the results with the experimental data, available from X-ray crystallography, allows, in particular, the rationalization of the importance of IL-15 key residues (e.g. Asp8, Lys10, Glu64). Furthermore, the pivotal role of water molecules in the stabilization of the various protein-protein interfaces and their H-bonds networks are underlined for each of the considered complexes.

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