Nearest-neighbor base sequences

Josse J., Kaiser A.D., Kornberg A. (1961). Enzymatic synthesis of deoxyribonucleic acid. VIII. Frequencies of nearest neighbor base sequence in deoxyribonucleic acid. J. Biol. Chem. 236 864-875. 

Specific base pairings There are two major types of bps in nucleic acids A T(U) and G C pairs. Because the stabilities of the two kinds of bps are different, generally the parameters Sa and Sg for A T(U) and G C pairs respectively, rather than a single s. The Sa and Sg are further dependent on at least the nearest-neighbor base sequence. 

In the previous section, the adaptation of the RIS model was based on the distance between next-nearest neighbor beads. This approach is obviously inadequate for CH3-CHX-CH2-CHX-CH3, because it necessarily abandons the ability to attribute different conformational characteristics to the meso and racemo stereoisomers. Therefore a more robust adaption of the RIS model to the 2nnd lattice is necessary if one wants to investigate the influence of stereochemical composition and stereochemical sequence on vinyl polymers [156]. Here we describe a method that has this capability. Of course, this method retains the ability to treat chains such as PE in which the bonds are subject to symmetric torsion potential energy functions. 

RNA has four kinds of bases along its polyribose-phosphate backbone and Tanaka assumes that only uracil is photochemically active, the other three bases being equivalently inert. In order to specify the statistical nature of the base sequence, the base composition and nearest neighbor frequencies are used, both of these being experimentally available quantities in many cases. If one assumes the sequence to be stationary, then ptt andpt, the probabilities that an arbitrarily given site is a uracil or an inert (photochemically) base, respectively, and the conditional probabilities, e.g., puu, suffice to represent the sequence. Because of the relations governing these probabilties, viz. 

Recall that the secondary-structure model for RNA is a model - and a crude one at that. It neglects pseudo knots and other tertiary interactions, does not take deviations from the additive nearest neighbor energy model into account, and is based on thermodynamic parameters extracted from melting experiments by means of multidimensional fitting procedures. Thus, you cannot expect perfect predictions for each individual sequence. Rather, the accuracy is on the order of 50% of the base pairs for the minimum free energy structure. 

In addition to the base-pairing disruption, this melting also destroys the stacking of bases in fixed orientations relative to one another that is observed in the duplex. Later, we will present an argument based upon thermodynamic measurements of the stabilities of synthetic oligonucleotides (small pieces of synthetic nucleic acids) that the next-nearest neighbor interactions observed in the base stacking sequence are a major contributor to the relative stabilities of duplexes. 

Figure 24. Local shape of value landscapes. Selective values as defined by Eqs. (IV.9)-(IV.ll) of 70 nearest neighbors surrounding a given reference sequence Ig are shown. Upper curve refers to evaluation according to third model for g = 1 as in Figure 22. Middle curve represents free energies according to second model evaluation. Lower curve counts numbers of base pairs in different folding patterns Free energy follows approximately number of base pairs, but excess production shows roughly opposite trend.

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