A series of aromatic fluorinated nucleosides the electrostatic surface potentials are depicted was used to probe electrostatic effects in the stacking of dna bases in water. Besides this, ss dna is completely devoid of random coil, base stacking, intrastrand hydrogen bonding and other types of pairing. Detailed knowledge of the time scales for breaking and forming individual base. Pdf statistical mechanics of base stacking and pairing in. Fluorinated dna bases as probes of electrostatic effects. Pdf trinucleotide base pair stacking free energy for. Dna base stacking involving adenine and 2aminopurine pdf. Characterization of the base stacking interactions in dna by means of lennardjones empirical potentials j. Experimentally, energetics of base stacking interactions in nucleic acids has been evaluated by studying the effect of dangling unpaired terminal bases on the overall stability of duplexes 35 and in the coaxial stacking hybridization experiments where binding of a short oligonucleotide to the singlestranded dna template is assisted by.
Purkinje university, kotlafska 2, 617 brno, czechoslovakia 2 institute of biophysics, czechoslovak academy of sciences. The latter study also investigated the performance of the m062x functional for stacked aa structures and found that it performed well. How significant is base stacking in the formation and. In terms of structural stability of nucleic acids in aqueous solution, the. Structural study shows that these phases are produced by the endtoend adhesion and consequent stacking of the duplex oligomers into polydisperse anisotropic rodshaped. Depending on the solution conditions and the local geometry of the dna these energies can be as high as 69 kcalmol per base pair. Free energy calculations for dna base stacking by replica. Understanding the roles of base stacking at the interface of stacked gquadruplexes is particularly important considering that highorder assemblies have been observed in vitro for telomeric dna and telomeric repeatcontaining rna terra 35,36, and that a number of gquadruplexbased aptamers are formed from stacked gquadruplexes 32,34,37. The enthalpies associated withd base stacking are favorable, while the entropy associated with the stacking of the bases is strongly unfavorable.
However, this destabilizing interaction is overcome by the favorable hydrogen bonding and base stacking interactions. Base stacking article about base stacking by the free. Base base and deoxyribose base stacking interactions in b dna and z dna. Jan 31, 2006 these parameters are obtained from the analysis of the melting data for dna polymers, dna oligomers 68 and dna dumbbells 9,10, and present the cumulative base pairing and stacking contribution of each dinucleotide stack to the overall stability of the molecule. A, b and z dna helix families david w ussery,danish technical university, lyngby, denmark there are three major families of dna helices. Different forms of viral dna molecules found in a variety of viruses are shown briefly in fig.
Singlemolecule dissection of stacking forces in dna science. Computational and experimental transhbond deuterium isotope shifts suggest that hbonding and electronic basestacking interactions, although largely orthogonal, are coupled in bform dna duplexes. Unlike previous approaches, this model describes thermal denaturation of dna secondary structure in the whole experimentally accessible temperature range. Ab initio quantum chemical calculations with inclusion of electron correlation effects significantly contributed to our understanding of molecular interactions of dna bases. Nov 11, 2016 inside the helix the bases are stacked one on top of the other. The negativelycharged phosphate groups in the backbone of the dna strands repel each other. Keywords stacking 2aminopurine adenine density functional theory dna bases.
Dna chain it undergoes a reaction with the 3 oh group to produce polydeoxynucleotide. More recently, coaxial stacking has been observed in higher order. Pdf basebase and deoxyribosebase stacking interactions in. In singlestranded dna ssdna, the forces involved in basestacking may be the primary determinants of secondary structure 20, whereas in. Apr, 2014 for more information, log on to this lecture explains the base stacking interaction of dna and the role of base stacking in. Determination of base binding strength and base stacking. For all temperatures and salt concentrations employed in present study, base stacking is the main stabilizing factor in the dna double helix. Frankkamenetskii center for advanced biotechnology and department of biomedical engineering, boston university, 36 cummington street, boston, ma 02215, usa. Water molecules have the ability to interact with themselves as well as with dna bases via dispersion, electrostatic, as well as hydrogen bonding.
Note, though, that a gc stacking interaction with the next base pair is geometrically different from a cg interaction. This is why the doublehelix structure is more stable than single strands. Free energy analysis and mechanism of base pair stacking in. A, b and zdna helix families david w ussery,danish technical university, lyngby, denmark there are three major families of dna helices. Pdf hydrogen bonding, base stacking, and steric effects in. Cooperativity effect on the base stacking interactions in. It has been known that the base stacking interactions contribute also to the dna stabilization 7 and the base stacking interactions demonstrated the sequencedependent property 24.
Dna molecules with solitary nicks flanked by all possible combinations of the base pairs we extract stacking parameters of the dna double helix. Unraveling base stacking driving forces in dna american. The da 18 dt 18 and dat 9 dat 9 duplexes have identical numbers of at. Direct measurements of base stacking interactions in dna by. Our understanding of dna and the way it is processed in biology would profit from improved knowledge about the elementary bonds in dna. Pdf basebase and deoxyribosebase stacking interactions. The potential energy surfaces of stacked structures consisting of adenine a and 2aminopurine 2ap have been investigated in the gas phase.
Need help with base stacking interactions in ssdnadsdna. Basebase and deoxyribosebase stacking interactions in bdna. Two pyrimidines thymie and cytosine and two purines adenine and guanine. So, i will try and answer the second part of your question, about maintenance. From ab initio calculations to molecular dynamics simulations. Bases or base pairs are planar, and these planes stack at contact distance about 3. Stacking interactions and intercalative dna binding uah. The individual bases form strong stacking interactions which are major contributors to duplex stability, as base stacking is much more prevalent in duplexes than in single strands.
Gc stacking interactions with adjacent bases tend to be more favorable. The double stranded dna molecule is held together by hyrodgen bonds. The stabilization amounts to almost 4 kcalmol and is thus. Dna dna deoxyribonucleic acid dna is the genetic material of all living cells and of many viruses. May 04, 2017 basestacking interactions in nucleic acid double strands are partly interstrand and partly intrastrand in nature. Aromatic base stacking another important interaction that stabilizes the dna structure is termed stacking and refers to the interaction between adjacent parallel aromatic bases. Base stacking and base pairing contributions into thermal stability of the dna double helix peter yakovchuk, ekaterina protozanova and maxim d.
The function of a dna polymerase is to form base pairs from an existing single template strand and free nucleotides in solution, and to do so with high specificity. Base stacking the degree of stabilization afforded by base stacking depends on the dna sequence. Dna, rna, replication, translation, and transcription. Dna is selfreplicating it can make an identical copy. Interstrand hydrogen bonding is clearly important in driving the formation of dna duplexes, but it is by no means the only contributing factor. Evaluating the contribution of base stacking during. Contribution of partial charge interactions and base stacking to the efficiency of primer extension at and beyond abasic sites in dna. Base pairing is described through a zipper model, base stacking through an ising model. In the file, simply ignore the zcoordinate of the base rings atoms, or the extended layer including exocyclic atoms, you get the projection of the atoms onto the mean base pair plane. Coaxial stacking was noted in the crystal structure of trnaphe.
Although some progress in the theoretical modeling of base stacking has been made 22,27 and some qualitative experimental results reported 26,28,29 as well as the very recent result concerning the base stacking in rna 30, direct measurements of base. Both facetoback the doublering system of one base exactly on top of that of the other one and facetoface one base flipped by 180 aa, 2ap2ap and a2ap stacks were considered. Some of the most important findings are introduced in the present overview. Basestacking and basepairing contributions into thermal. Jan 01, 2006 overall stability, stacking and base pairing contributions for dna polymers at different salt conditions. This difference is due to the greater anharmonicity of the n3. Although hydrogen bonding interactions between dna bases has been extensively studied theoretically, stacking interactions remain difficult to predict and require application of higher and more costly levels of theory. Pdf hydrogen bonding, base stacking, and steric effects. However, description of stacking association in condensed phase and understanding of the stacking role in biomolecules remain a difficult problem, as the net base stacking forces always act in a complex and context.
The stacking free energies of nucleic acid bases, nucleosides, nucleotides in aqueous solution have been determined by a number of experimental measurements. Further, nucleic acid bases interact with solvent molecules, metal cations, drugs, and other species. Stacking can also regulate the overall geometry of dna strands. We propose a statistical mechanics model for dna melting in which base stacking and pairing are explicitly introduced as distinct degrees of freedom. Cooperativity effect on the base stacking interactions in dna. Coaxial stacking occurs when two rna duplexes form a contiguous helix, which is stabilized by base stacking at the interface of the two helices. Interplay of electrostatic, basepairing, and basepair stacking interactions previous article aggregation of nucleosomes by divalent cations next article spectral inhomogeneity of photosystem i and its influence on excitation equilibration and trapping in the cyanobacterium synechocystis sp. Base stacking effects are especially important in the secondary structure and tertiary structure of rna. In fact, dna melting experiments do not allow separation of the two. Kypr2 1 department of physical electronics, faculty of natural sciences, j. Purines and pyrimidines dna and rna are made up of.
Aug 25, 2005 further evidence that base stacking governs singlet excited states in dna base multimers is shown in fig. Although increasing fluorine substitution from zero through five generally increases stacking ability, a new tetrafluorinated analogue is, surprisingly, the strongest helix stabilizer, while the. These interactions are important in nucleobase stacking within dna and rna molecules, protein folding, templatedirected synthesis, materials science, and molecular recognition, although new research suggests that pi stacking may not be. Nov 23, 2007 short complementary bform dna oligomers, 6 to 20 base pairs in length, are found to exhibit nematic and columnar liquid crystal phases, even though such duplexes lack the shape anisotropy required for liquid crystal ordering. This interaction results from sharing the electron clouds of the aromatic rings. Base stacking configuration is a major determinant of excited state. Thermal denaturation methods 5, beacon kinetics 6 and mechanical unzipping 7, were used to estimate stacking free energies in singlestranded dna. Coaxial stacking, otherwise known as helical stacking, is a major determinant of higher order rna tertiary structure. Base pairing, base stacking and nucleic acid structure. Endtoend stacking and liquid crystal condensation of 6 to. The locations of the stationary points on the potential energy surface differ for the three different systems. The genetic code is the sequence of bases on one of the strands. More recently base stacking interactions were measured in dna fragments with a higher number of base pairs as well.
Dna base stacking involving adenine and 2aminopurine. Inside the helix the bases are stacked one on top of the other. These studies show that, at the cbs limit, mp2 overestimates the interaction. Using a combination of bulk and singlemolecule techniques, we measure the structural and mechanical properties of two dnas which differ in both sequence and basestacking arrangement in aqueous buffer, as revealed by circular dichroism. Stacking interactions and the twist of dna journal of. A gene is a specific sequence of bases which has the information for a particular protein. Characterization of the base stacking interactions in dna. The stability of the dna double helix depends on a fine balance of interactions including hydrogen bonds between bases, hydrogen bonds between bases and surrounding water molecules, and base stacking interactions between adjacent bases.
Jun 20, 20 however, description of stacking association in condensed phase and understanding of the stacking role in biomolecules remain a difficult problem, as the net base stacking forces always act in a complex and context. The orientation of adjacent base pairs such that their planes are parallel and their surfaces almost touch, as occurs in doublestranded deoxyribonucleic. The stability of the dna and rna double helix arises from a fine balance of hydrogen h bonding interactions between complementary bases. Pdf hydrogen bonding, stacking and cation binding of dna. Stability of dna double helix conferred by base stacking. I have read a lot about base stacking ability to stabilize ds dna and how theyre more important than hydrogen bonding. T base pair, the hbond is shorter and stronger in the rar. Introduction pictures of the double helix of deoxyribonucleic acid. In this letter, we present and discuss the results of singlemolecule elasticity mea. For all temperatures and salt concentrations employed in present study, basestacking is the main stabilizing factor in the dna double helix. Moreover, the stacking forces are balanced with many other energy contributions. Stacking is a iffusion controlled, additive, and stabilized by weak forces. Base stacking interaction is a major factor stabilizing the threedimensional structure of dna. Base stacking and pairing, accurate calculations, molecular interactions, dna.
Direct measurements of base stacking interactions in dna. Base stacking is a common arrangement of nucleobases found in the three dimensional structure of nucleic acids. The final 2feature of the molecule is a nitrogen base. Statistical mechanics of base stacking and pairing in dna. Nature and magnitude of aromatic base stacking in dna and rna. A great example of how vdw energy depends on the highest possible degree of surface contact is the difference in stacking energy of a 5gc35gc3 helix which is almost. Mar 16, 2015 it has been known that the base stacking interactions contribute also to the dna stabilization 7 and the base stacking interactions demonstrated the sequencedependent property 24. Endtoend stacking and liquid crystal condensation of 6. Unraveling base stacking driving forces in dna the.
Base stacking controls excitedstate dynamics in at dna. Base stacking is a key determinant of nucleic acid structures, but the precise origin of the thermodynamic driving force behind the. Basestacking and basepairing contributions into thermal stability of. The stacking reaction is overall favorable, however, since the entropy and enthalpy of the solvent are both strongly favorable. The helical structure of dna is variable and depends on the sequence as well as the environment. The interaction is slightly stronger in purines, which possess a double ring. The structural stability of the dna double helix sciencing. Typical scatchard plots representing the the overall stacking pattern.
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