Thermodynamic stability sequence dependent

Double-crossover molecules have been used extensively to characterize the properties of Holliday junctions. The strong torsional coupling between their crossover points has been exploited to construct symmetric immobile junctions (S. Zhang et al. 1993), junctions in which one of the crossovers is flanked by homology, but is nevertheless unable to branch migrate. Symmetric immobile junctions have been used to characterize crossover isomerization thermodynamics (S. Zhang and Seeman 1994) and, more recently, the sequence dependence of the branch point stability (W. Sun et al., 1998). Double crossover molecules have also been employed to establish the cleavage patterns of endonuclease VII, an enzyme that resolves branched junctions (Fu et al. 1994 a). 

The thermodynamic stability (melting) of DNA containing an AP is markedly reduced (Gelfand et al. 1998). In a 13-mer DNA duplex, this lesion does not alter the global B-form conformation, but it induces a significant enthalpic destabilization of the duplex the amount of which being strongly dependent on the base sequence. 

The DNA lesion 8,5 -cyclo-2 -dG, formed by attack of hydroxyl radicals, contains damage to both base and sugar, and is therefore repaired by nucleotide excision repair enzymes, and is involved in diseases with defective nucleotide excision repair. A mass spectroscopic assay has been developed for the quantitation of the lesion after enzymatic separation of the 5 (R) and 5 (S) isomers. The thermodynamic stability of ODNs containing the oxidative lesion, 2-hydroxy-dA has been examined. It was shown that when the lesion was in the middle of a DNA duplex it behaved as a universal base, in that there was no dilference in Tm when opposite any of the canonical bases. On the other hand, when it was near the termini, there was a preference for base pairing with thymidine, but it also formed base pairs with other nucleotides which was sequence dependent. The extent of oxoprenylation by malondialdehyde or adenine propenal has been investigated in DNA, see (139). ssDNA was found to be more sensitive to oxoprenylation, and supercoiled-DNA more susceptible than linearised plasmid DNA. A variety of intercalators were used, some of which inhibit oxoprenylation, e.g. netropsin, whilst others, like ethidium bromide, caused enhanced oxoprenylation. 

It is easy to calculate the MFE as a measure of thermodynamic stability for a sequence using, e.g., RNAfold (9). However, the MFE depends on the length and the base composition of the sequence and is, therefore, difficult to interpret in absolute terms. RNAz calculates a normalized measure of thermodynamic stability by comparing the MFE m of a given (native) sequence to the MFEs of a large number of random sequences of the same length and base composition. A z-score is calculated as z = (m — p)/o where p and cr are the mean and standard deviations, respectively, of the MFEs of the random samples. Negative z-scores indicate that a sequence is more stable than expected by chance. RNAz does not actually sample random sequences but approximates z-scores, which is faster but of the same accuracy. 

We first consider why base sequence effects can affect the thermodynamic stabilities of double-stranded DNA. The neighboring base-base stacking energies have been analyzed in detail (e.g., see [116, 117]). These interactions are base sequence dependent because of potential steric clashes and electrostatic effects between the... 

In sunmary, a model for G-C destabilization has been derived from nucleotide hydrogen exchange studies that is consistent with thermodynamic considerations of H-bond strength and DN4 stability. This model contains the point of view that DN4 stability may depend on the weakness of the interbase oxygen-to-amino H-bonds If the nucleobase aminos were strong H-bond donors a stable double helix could not be formed, due to the competition of water for the donor sites. Sequence specific interactions of protein cationic sidechains, or non-specific interactions of small cations, both with the G(N-7) site accessible to solvent in the large helical groove, would decrease the interbase proton lifetime and allow a drastic increase in solvent (water) interaction of G-C-rich sequences exclusively. A central feature of the model s extension, the requirement for simultaneous interaction of... 

The thermodynamic stability, the aggregation state, and the relative orientation of the helical strands in such peptides were shown to depend largely on the identity of the amino acid residues at positions a, d, e, and g. The use of leucine and valine at the hydrophobic core (positions a and glutamic acid and lysine at the e and g positions were shown to control equilibrium between dimeric and trimeric coiled-coil aggregation states." Peptide sequences that allow interconversion between dimeric and trimeric parallel coiled coils were found as productive templates to enhance substrate selectivity, catalytic efficiency, and turnover and were commonly used in peptide-replicating systems. 

A recent nanosecond range MD simulation on the DNA duplex d(CGCGAATTCGCG)2, based on the AMBER 4.1 force-field and the PME method, confirmed independently the stability of B-form duplexes under these simulation conditions. The authors observed an intrusion of a Na counterion in the DNA minor groove at an ApT step termed subsequently the ApT pocket . They concluded that such ion intrusion in DNA minor grooves may influence thermodynamical and structural DNA properties in a sequence-dependent manner. The dynamical properties as well as the hydration of the B-form d(CCAACGTTGG)2 decamer, shown to be stable in the nanosecond range, were investigated by Cheatham et al. ... 

Termination positions are defined by the thermodynamic stability of the polymerase complex, whereas the efficiencies of termination are determined by a kinetic competition between RNA elongation and release at each position (94). The termination efficiency is affected mostly by the strength of the stem—loop, the presence of the U-tract, and also by the concentration of NTP substrates. The efficiency of transcription termination also depends on other factors such as the size and shape of the hairpin, not just its stability, most likely involving interactions with the polymerase. Different RNA hairpins exert varying effects on transcription termination, while a cruciform structure may have no or some attenuating effect on transcription. Furthermore, certain changes in the stem sequence designed to maintain or raise the stability of the stem (AG = —18 kcal/mol) lead to a decrease... 

The preference has both thermodynamic and structural reasons. Initially the sequence dependence of the hairpin-loop thermodynamic stability was attributed... 

On heating from a crystalline phase, DOBAMBC melts to form a SmC phase, which exists as the thermodynamic minimum structure between 76 and 95°C. At 95°C a thermotropic transition to the SmA phase occurs. Finally, the system clears to the isotropic liquid phase at 117°C. On cooling, the SmC phase supercools into the temperature range where the crystalline solid is more stable (a common occurrence). In fact, at 63°C a new smectic phase (the SmF) appears. This phase is metastable with respect to the crystalline solid such phases are termed monotropic, while thermodynamically stable phases are termed enantiotropic. The kinetic stability of monotropic LC phases is dependent upon purity of the sample and other conditions such as the cooling rate. However, the appearance of monotropic phases is typically reproducible and is often reported in the phase sequence on cooling. It is assumed that phases appearing on heating a sample are enantiotropic. 

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