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1.
Estimation of the diversity between DNA calorimetric profiles,differential melting curves and corresponding melting temperatures
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Chun‐Ling Chang Alexander S. Fridman Inessa E. Grigoryan Elena N. Galyuk Oleg N. Murashko Chin‐Kun Hu Dmitri Y. Lando 《Biopolymers》2016,105(11):832-839
The Poland–Fixman–Freire formalism was adapted for modeling of calorimetric DNA melting profiles, and applied to plasmid pBR 322 and long random sequences. We studied the influence of the difference (HGC?HAT) between the helix‐coil transition enthalpies of AT and GC base pairs on the calorimetric melting profile and on normalized calorimetric melting profile. A strong alteration of DNA calorimetrical profile with HGC?HAT was demonstrated. In contrast, there is a relatively slight change in the normalized profiles and in corresponding ordinary (optical) normalized differential melting curves (DMCs). For fixed HGC?HAT, the average relative deviation (S) between DMC and normalized calorimetric profile, and the difference between their melting temperatures (Tcal?Tm) are weakly dependent on peculiarities of the multipeak fine structure of DMCs. At the same time, both the deviation S and difference (Tcal?Tm) enlarge with the temperature melting range of the helix‐coil transition. It is shown that the local deviation between DMC and normalized calorimetric profile increases in regions of narrow peaks distant from the melting temperature. 相似文献
2.
In this paper we analyze theoretically the observable details of the differential melting curves (DMC) and the denaturation maps (DM) of a DNA. With the help of a mathematical model, we explore their implications, their relation with each other and with the genetic map of the molecule, and discuss possible future applications. ?X174 is used as the example, since its sequence and genetic map are available. We find that each gene section of ?X174 has a characteristic DMC. A reconstruction scheme to get the DMC of a whole piece from those of its constituent genes is shown to be fairly successuful. The relations between the melting curve and the denaturation maps are clarified. We observe that nearly always, the beginning and end of a gene melt at lower temperatures. The sharp features in the DM indicate that despite the long-range cooperative interactions, the DM do reflect the local sequence effect. Denaturation maps (theoretical) of ?X174 and SV40 are presented. From available data of other authors, we estimate that the dependence of the melting temperature tm on GC, the fraction of (G+C)-content, and on x, the ionic concentration in fractions of the standard saline citrate solution, can be expressed as tm(x, GC) = -5.2 (log x)GC + 18.4 log x + 41.0GC + 69.4. The first two coefficients are less certain. 相似文献
3.
The effects of aqueous neutral-salt solutions on the melting temperatures of deoxyribonucleic acids 总被引:10,自引:0,他引:10
The helical stability of a variety of DNA samples, ranging in base composition from 0 to 72 mole-% GC, has been studied by heat denaturation at neutral pH in increasing concentrations of LiCl, NaCl, KCl, CsCl, Li2SO4, and K2SO4. The variation of melting temperature with average base composition, dTm/dXGC, was found to decrease drastically in the concentrated salt media, e.g., from 41°C in 0.006M LiCl to 29°C in 3.2M LiCl, and from 39°C in 0.003M Li2SO4 to 18°C in 1.6M Li2SO4. At the same time, the thermal transition is much more cooperative in the concentrated salt solutions than at low ionic strength. Indeed, at limiting salt concentrations, the transition breadth seems to reach a minimum value irrespective of the compositional heterogeneity of the DNA samples. Attempts to correlate the observed decrease of dTm/dXGC with predicted changes in the enthalpy of melting, deduced from a simple theoretical treatment, experimental data on the binding of counterions and water to DNA, and experimental data on thermal denaturation, were unsuccessful. However, the strongly reduced composition dependence of the melting temperature can be understood in terms of a destabilizing effect of the concentrated salt media on GC-base pairs. It is suggested, though not proven, that the destabilization involves the displacement of water molecules from the DNA helix. 相似文献
4.
Equilibrium properties of heterogeneous DNA near the melting temperature Tm are investigated using the grand partition function. The present approach gives exact and analytical solutions. The algebraic expressions enhance a more thorough understanding of the correlation among many observed equilibrium phenomena. The following quantities have been examined: melting temperature Tm, transition width W, partial melting curves θAT and θGC, mean length of a helical segment h, and correlation length γ. 相似文献
5.
Effect of ionic conditions on DNA melting curve parameters 总被引:1,自引:0,他引:1
6.
Dmitri Y. Lando Alexander S. Fridman Chun-Ling Chang Inessa E. Grigoryan Elena N. Galyuk Oleg N. Murashko Chun-Chung Chen Chin-Kun Hu 《Analytical biochemistry》2015
Many factors that change the temperature position and interval of the DNA helix–coil transition often also alter the shape of multi-peak differential melting curves (DMCs). For DNAs with a multi-peak DMC, there is no agreement on the most useful definition for the melting temperature, Tm, and temperature melting width, ΔT, of the entire DNA transition. Changes in Tm and ΔT can reflect unstable variation of the shape of the DMC as well as alterations in DNA thermal stability and heterogeneity. Here, experiments and computer modeling for DNA multi-peak DMCs varying under different factors allowed testing of several methods of defining Tm and ΔT. Indeed, some of the methods give unreasonable “jagged” Tm and ΔT dependences on varying relative concentration of DNA chemical modifications (rb), [Na+], and GC content. At the same time, Tm determined as the helix–coil transition average temperature, and ΔT, which is proportional to the average absolute temperature deviation from this temperature, are suitable to characterize multi-peak DMCs. They give smoothly varying theoretical and experimental dependences of Tm and ΔT on rb, [Na+], and GC content. For multi-peak DMCs, Tm value determined in this way is the closest to the thermodynamic melting temperature (the helix–coil transition enthalpy/entropy ratio). 相似文献
7.
Nirmal Kumar Mishra 《Molecular biology reports》1979,4(4):241-246
The structure of ribosomal DNA (rDNA) satellite of sea urchin (Lytechinus variegatus) sperm has been re-examined after purification by two widely used methods. Saturation hybridization experiments indicate that about 28–32% of the rDNA contain sequences complementary to rRNA. Results of hyperchromic spectral analysis reveal that the rDNA melts as two distinct but unequal components. The early transition presumably corresponds to the melting of most of the transcribed part and the late transition is suggestive of the melting of a G+C-rich segment of the rDNA, which may be a non-transcribed spacer.Abbreviations FAT
fraction of all A+T pairs denatured
- FGC
fraction of all G+C pairs denatured
- SSC
standard saline citrate
- rDNA
template for ribosomal RNA
This work is a part of the author's Ph.D. thesis (U.N.C., Chapel Hill). 相似文献
8.
Equations were determined for the dependency of the melting temperature (Tm) of DNA upon the logarithm of the sodium ion concentration, for four DNA samples of widely different base compositions (θGC). The slopes of these Tm versus log M equations wore found to decrease with increasing θG Cof the samples. An empirical equation relating Tm, log M (Na+) and θG C was derived, which also accounts for differences in Tm versus log M slopes. Data from the literature for some synthetic polynucleotides and for the crab(Cancer pagarus) satellite poly AT are discussed in relation to the above finding. The changes in Tm versus log M slopes with θG C are interpreted in terms of changes in the thermodynamic parameters ΔS and ΔH with base composition. 相似文献
9.
V. V. Anshelevich A. V. Vologodskii A. V. Lukashin M. D. Frank-Kamenetskii 《Biopolymers》1984,23(1):39-58
We treat the problem of the mean time of complete separation of complementary chains of a duplex containing N base pairs. A combination of analytical and computer methods is used to obtain the exact solution in the form of a compact expression. This expression is used to analyze the limits of application of the equilibrium theory of helix–coil transition in oligo- and polynucleotides. It also allows the melting behavior of a biopolymer to be predicted when its melting is nonequilibrium. In the case of oligonucleotides for which the equilibrium melting takes place at a high value of the stability constant s, the general expression turns into the equation of Craig, Crothers, and Doty, used by them to determine the rate constant kf of the growth of a helical region from temperature-jump experiments. For the case of fragmented DNA with N ~ 102, the melting process is shown to be completely nonequilibrium, and as a result, the observed melting temperature should be higher than that for the equilibrium. A simple equation is obtained that makes possible calculation of the real, “kinetic” melting temperature Tk. As N increases, the observed melting temperature should approach the equilibrium value, Tm. This analysis has explained quantitatively the peculiar chain-length dependence of the experimentally observed shift in the DNA melting temperature during fragmentation. A thorough analysis is given of the nonequilibrium effects in the melting process of long DNA molecules (N ? 103). The main conclusion is that even in the presence of profound hysteresis phenomena, the melting profile observed on heating may differ only slightly from the equilibrium profile. 相似文献
10.
Interaction between polylysine and DNA's of varied G + C contents was studied using thermal denaturation and circular dichroism (CD). For each complex there is one melting band at a lower temperature tm, corresponding to the helix–coil transition of free base pairs, and another band at a higher temperature t′m, corresponding to the transition of polylysine-bound base pairs. For free base pairs, with natural DNA's and poly(dA-dT) a linear relation is observed between the tm and the G + C content of the particular DNA used. This is not true with poly(dG)·poly(dC), which has a tm about 20°C lower than the extrapolated value for DNA of 100% G + C. For polylysine-bound base pairs, a linear relation is also observed between the t′m and the G + C content of natural DNA's but neither poly(dA-dT) nor poly(dG)·poly(dC) complexes follow this relationship. The dependence of melting temperature on composition, expressed as dtm/dXG·C, where XG·C is the fraction of G·C pairs, is 60°C for free base pairs and only 21°C for polylysine-bound base pairs. This reduction in compositional dependence of Tm is similar to that observed for pure DNA in high ionic strength. Although the t′m of polylysine-poly(dA-dT) is 9°C lower than the extrapolated value for 0% G + C in EDTA buffer, it is independent of ionic strength in the medium and is equal to the tm0 extrapolated from the linear plot of tm against log Na+. There is also a noticeable similarity in the CD spectra of polylysine· and polyarginine·DNA complexes, except for complexes with poly(dA-dT). The calculated CD spectrum of polylysine-bound poly(dA-dT) is substantially different from that of polyarginine-bound poly(dA-dT). 相似文献
11.
Employing a set of 43 othologous mouse and rat genes, Hughes and Yeager (J. Mol. Evol. 45:125–130, 1997) reported (1) no correlation between synonymous and nonsynonymous rates of nucleotide substitution, (2)
a positive correlation between intronic GC contents (GC
i) and intronic substitution rates (K
i), (3) that the average K
i value was very similar to the average K
s value, and (4) that the compositional correlation between the rat and the mouse genes is stronger at the third codon position
(GC3) than at the first and second codon positions (GC12). We have examined the robustness of these results to alterations in substitution rate estimation protocol, alignment protocol,
and statistical procedure. We find that a significant correlation between K
a and K
s is observed either if a rank correlation statistic is used instead of regression analysis, if one outlier is excluded from
the analysis, or if a regression weighted by gene size is employed. The correlation between K
i and GC
i we find to be sensitive to changes in alignment protocol and disappears on the use of weighted means. The finding that K
s and K
i are approximately the same is dependent on the method for estimating K
s values. Finally, the variance around the regression line of rat GC3 versus mouse GC3 we find to be significantly higher than that in GC12. The source of the discrepancy between this and Hughes and Yeager's result is unclear. The variance around the line for GC4 is higher still, as might be expected. Using a methodology that may be considered preferable to that of Hughes and Yeager,
we find that all four of their results are contradicted. More importantly this analysis reinforces the need for caution in
assembling and analyzing data sets, as the degree of sensitivity to what many might consider minor methodological alterations
is unexpected.
Received: 2 February 1998 / Accepted: 23 March 1998 相似文献
12.
Thermal denaturation of direct-mixed and reconstituted polylysine–DNA complexes in 2.5 × 10?4 M EDTA, pH 8.0 and various concentrations of NaCl has been studied. For both complexes, increasing ionic strength of the solution raises Tm, the melting temperature of free base pairs. The linear dependence of Tm on log Na+ indicates that the concept of electrostatic shielding on phosphate lattice of an infinitely long pure DNA by Na+ can be applied to short free DNA segments in a nucleoprotein. For a direct-mixed polylysine–DNA complex, the melting temperature of bound base pairs Tm′ remains constant at various ionic strengths. On the other hand, the Tm′ in a reconstituted polylysine–DNA complex is shifted to lower temperature at higher ionic strength. This phenomenon occurs for reconstituted complex with long polylysine of one thousand residues or short polylysine of one hundred residues. It is shown that such a decrease of Tm′ is not due to a reduction of coupling melting between free and bound regions in a complex when the ionic strength is raised. It is also not due to intermolecular or intramolecular change from a reconstituted to a direct-mixed complex. It is suggested that this phenomenon is due to structural change on polylysine-bound regions by ionic strength. It is suggested further that Na+ may replace water molecules and bind polylysine-bound regions in a reconstituted complex. Such a dehydration effect destabilizes these regions and lowers Tm′. This explanation is supported by circular dichroism (CD) results. 相似文献
13.
The objective of the present investigation was to improve the dissolution rate of Rofecoxib (RXB), a poorly water-soluble
drug by solid dispersion technique using a water-soluble carrier, Poloxamer 188 (PXM). The melting method was used to prepare
solid dispersions. A 32 full factorial design approach was used for optimization wherein the temperature to which the melt-drug mixture cooled (X
1) and the drug-to-polymer ratio (X
2) were selected as independent variables and the time required for 90% drug dissolution (t90) was selected as the dependent variable. Multiple linear regression analysis revealed that for obtaining higher dissolution
of RXB from PXM solid dispersions, a low level ofX
1 and a high level ofX
2 were suitable. The differential scanning calorimetry and x-ray diffraction studies demonstrated that enhanced dissolution
of RXB from solid dispersion might be due to a decrease in the crystallinity of RXB and PXM and dissolution of RXB in molten
PXM during solid dispersion preparation. In conclusion, dissolution enhancement of RXB was obtained by preparing its solid
dispersions in PXM using melting technique. The use of a factorial design approach helped in identifying the critical factors
in the preparation and formulation of solid dispersion.
Published: April 13, 2007 相似文献
14.
Dmitri Y. Lando Alexander S. Fridman Roger Wartell 《Journal of biomolecular structure & dynamics》2013,31(4):519-531
Abstract DNA chemical modifications caused by the binding of some antitumor drugs give rise to a very strong local stabilization of the double helix. These sites melt at a temperature that is well above the melting temperatures of ordinary AT and GC base pairs. In this work we have examined the melting behavior of DNA containing very stable sites. Analytical expressions were derived and used to evaluate the thermodynamic properties of homopolymers DNA with several different distributions of stable sites. The results were extended to DNA with a heterogeneous sequence of AT and GC base pairs. The results were compared to the melting properties of DNA with ordinary covalent interstrand cross-links. It was found that, as with an ordinary interstrand cross-link, a single strongly stabilized site makes a DNA's melting temperature (Tm ) independent of strand concentration. However in contrast to a DNA with an interstrand cross-link, a strongly stabilized site makes the DNA's Tm independent of DNA length and equal to T ∞, the melting temperature of an infinite length DNA with the same GC-content and without a stabilized site. Moreover, at a temperature where more than 80% of base pairs are melted, the number of ordinary (non-modified) helical base pairs (n) is independent of both the DNA length and the location of the stabilized sites. For this condition, n(T) = (2ω-a) S (1- S ) and S = exp[ΔS(T∞-T)/(RT)] where ω is the number of strongly stabilized sites in the DNA chain, a is the number of DNA ends that contain a stabilized site, and ΔS, T, and R are the base pair entropy change, the temperature, and the universal gas constant per mole. The above expression is valid for a temperature interval that corresponds to n<0.2N for ω=1, and n<0.1N for ω>1, where N is the number of ordinary base pairs in the DNA chain. 相似文献
15.
Helix-coil transitions in nucleoprotein at low salt concentrations are known to be characterized by two phases of the process: independent melting of uncomplexed “naked” regions without rearrangement of proteins, followed, at higher temperatures, by melting of complexed DNA. Blocking at the ends of these regions increases their thermal stability and three is a shift of 10–20°C in tm of the melting profiles. In this study the basic assumption is that the loop entropy effect is mainly responsible for such stabilization. Calculations are made using conventional h-c transition theory for a system of independently melted segments with fixed ends. Segments are either homosize or have randomly distributed lengths. Calculated melting curves are used to obtain tm, and transition width-dependence on segment length (or average length when randomly distributed) and on the nucleation parameter σ. Base-pair heterogeneity is taken into account by averaging over different base-pair distributions in the individual segments, using Gaussian distribution around the overall (G+C)-content. It is shown that this causes only an additional widening of the transition but no additional tm shift. Comparison is made with similar systems in the literature. The main conclusion drawn is that the treatment proposed may be useful for analysis of the lower temperature melting phase in nucleoprotein at low counterion concentrations. It may be used as an independent method to reveal the features of nucleoprotein structure. 相似文献
16.
The ribosomal RNA from several stocks of the genera Leishmania and Trypanosoma were studied by gel electrophoresis, sedimentation on sucrose density gradients and RNA/DNA hybridization experiments. Three major components were observed after electrophoresis in polyacrylamide gels (PAGE-SDS), the relative molecular masses being respectively: X1= 0.83 megadaltons, X2= 0.63 megadaltons and X3= 0.54 megadaltons for Leishmania RNA; and X1= 0.86 megaldaltons, X2= 0.78 megadaltons, and X3= 0.58 megadaltons for Trypanosoma RNA. Depending upon the isolation procedure, a fourth component. X0= 1.2 megadaltons (26S), became evident. The later component was purified from Leishmania brasiliensis (Y) by centrifugation on a linear 15-30% sucrose density gradient. This component, after heat denaturation and PAGE-SDS, gave rise to two bands coinciding in molecular mass with those of X2 and X3 indicating that these components are part of the large ribosomal subunit whereas X1 belongs to the small one. The above mentioned differences in mobilities of components X1 and X2 between the two genera were no longer observed after electrophoresis in denaturing agarose-formaldehyde gels, suggesting secondary structural differences among these RNA species. Hybridization experiments with L. brasiliensis (Y) DNA showed that both RNA types compete equally well for the ribosomal sites in this DNA, and that L. brasiliensis (Y) rRNA recognizes the ribosomal sites in DNA of Trypanosoma cruzi (EP), thus indicating that no gross changes occurred in their nucleotide sequences during evolution. 相似文献
17.
G. F. Korytina L. Z. Akhmadishina D. G. Yanbaeva T. V. Victorova 《Molecular Biology》2006,40(2):200-206
Allele and genotype frequency distributions of the vitamin D-binding protein gene (DBP) were studied in patients with chronic obstructive pulmonary disease (COPD, N = 298) and healthy individuals (N = 237) from two ethnic groups (Tatars and Russians) resident in the Republic Bashkortostan. The DBP genotype frequency distribution significantly differed between Tatars and Russians (X 2 = 8.854, df = 5, P = 0.04). The DBP allele frequency distribution was similar in healthy subjects of both ethnic groups, with allele frequency decreasing as GC*1S > GC*1F > GC*2. The most common DBP genotype was GC*1F/1S in Tatars (36.79%) and GC*1S/2 in Russians (34.62%). It was demonstrated that, in Tatars, the genotype GC*1F/1S is protective against COPD, its frequency being significantly lower in COPD patients than in healthy subjects (19.85% vs. 36.79%; X 2 = 7.622, P = 0.0067, P cor = 0.0335; OR = 0.42, 95%CI 0.42–0.95). On the other hand, the genotype GC*1F/2 was more common among COPD patients than among healthy individuals (19.08% vs. 8.49%; X 2 = 4.52, P = 0.033, P cor = 0.165; OR = 2.54, 95%CI 1.067–6.20). No differences in DBP genotype and allele frequency distributions was found between COPD patients and healthy individuals in the Russian population. 相似文献
18.
J. Monaselidze G. Majagaladze Sh. Barbakadze D. Khachidze M. Gorgoshidze Y. Kalandadze 《Journal of biomolecular structure & dynamics》2013,31(4):419-424
Abstract Thermodynamic parameters of melting process (δHm, Tm, δTm) of calf thymus DNA, poly(dA)poly(dT) and poly(d(A-C))·poly(d(G-T)) were determined in the presence of various concentrations of TOEPyP(4) and its Zn complex. The investigated porphyrins caused serious stabilization of calf thymus DNA and poly poly(dA)poly(dT), but not poly(d(A-C))poly(d(G-T)). It was shown that TOEpyp(4) revealed GC specificity, it increased Tm of satellite fraction by 24°C, but ZnTOEpyp(4), on the contrary, predominately bound with AT-rich sites and increased DNA main stage Tm by 18°C, and Tm of poly(dA)poly(dT) increased by 40 °C, in comparison with the same polymers without porphyrin. ZnTOEpyp(4) binds with DNA and poly(dA)poly(dT) in two modes—strong and weak ones. In the range of r from 0.005 to 0.08 both modes were fulfilled, and in the range of r from 0.165 to 0.25 only one mode—strong binding—took place. The weak binding is characterized with shifting of Tm by some grades, and for the strong binding Tm shifts by ~ 30–40°C. Invariability of ΔHm of DNA and poly(dA)poly(dT), and sharp increase of Tm in the range of r from 0.08 to 0.25 for thymus DNA and 0.01–0.2 for poly(dA)poly(dT) we interpret as entropic character of these complexes melting. It was suggested that this entropic character of melting is connected with forcing out of H2O molecules from AT sites by ZnTOEpyp(4) and with formation of outside stacking at the sites of binding. Four-fold decrease of calf thymus DNA melting range width ΔTm caused by increase of added ZnTO- Epyp(4) concentration is explained by rapprochement of AT and GC pairs thermal stability, and it is in agreement with a well-known dependence, according to which ΔT~TGC-TAT for DNA obtained from higher organisms (L. V. Berestetskaya, M. D. Frank-Kamenetskii, and Yu. S. Lazurkin. Biopolymers 13, 193–205 (1974)). Poly (d(A-C))poly(d(G-T)) in the presence of ZnTOEpyp(4) gives only one mode of weak binding. The conclusion is that binding of ZnTOEpyp(4) with DNA depends on its nucleotide sequence. 相似文献
19.
KATSUMA DAN SHOJI TANAKA KIMIE YAMAZAKI YOSHIHIRO KATO 《Development, growth & differentiation》1980,22(3):589-598
Cell cycles have been analyzed in 10 divisions up to the time of hatching in the embryos of the sea urchin, Hemicentrotus pulcherrimus. In the first 5 cleavages, division synchrony is very high. On the average, TGC= 55.4 min, TG1= 0 min, Ts= 12 min, TG2=±0 min, TM= 42 min. In the remaining 5 cleavages, TGC becomes longer: 70 min for the 7th to 246 min for the 10th cleavage. G1 and G2 become definitely recognizable and become longer along with Ts. TM stays more or less constant. Plots of the changing lengths of the four compartments (G1, S, G2, M) on the Y-axis against TGC (X-axis) can be fitted to the following 4 regression equations; TG1= 0.28TGC - 19.7, Ts= 0.609TGC - 15.2, TG2= 0.104TGC - 4.72 and TM= 0.007TGC+ 39.6. 相似文献
20.
Unwinding kinetics of cooperatively melting regions in DNA 总被引:2,自引:0,他引:2
Unwinding of a single cooperatively melting region of ColE1 DNA is investigated by a slow temperature jump in formamide–neutral buffer mixed solvent. The semilogarithmic plots of unwinding relaxation curves show a marked terminal linear region following the fast decay, which occurred within the temperature rise time (1 ~ 2 s). This longest relaxation is ascribed to the total unwinding of a single cooperatively melting region. The longest relaxation time, τ1, is uniquely determined by the final equilibrium state and becomes shorter as the final temperature increases. Decrease in ionic strength makes τ1 and its fractional amplitude increase, and the relaxation almost approaches single-exponential decay. The facts that (1) τ1 of a single cooperatively melting region whose unwinding suffers larger frictional resistance does not always unwind more slowly, as was shown by the observations of τ1's of almost the same cooperatively melting region located at different positions on two linearized ColEl DNAs and of τ1's of two cooperatively melting regions on the same linearized ColEl DNA; (2) τ1 has strong dependence on the equilibrium state after a temperature jump; and (3) the observed τ1 is much longer than the expected time of the frictional barrier all demonstrate that the τ1 is limited by chemical but not hydrodynamic processes. The detailed unwinding process of a single cooperatively melting region, elucidated by evidence of a negative apparent activation energy of the rewinding process and by extensive computer simulation of the equilibrium melting process, suggests that the local heterogeneity of G+C content in a cooperatively melting region, as well as its averaged G+C content, strongly affects its unwinding rate. The present study of a single cooperatively melting region is found to be useful to improve our understanding of the detailed mechanism of complex unwinding of large natural DNAs, in which many cooperatively melting regions unwind. 相似文献