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Correlation of T m and sequence of DNA duplexes with Δ H computed by an improved empirical potential method
Author(s) -
Ornstein Rick L.,
Fresco Jacques R.
Publication year - 1983
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360220811
Subject(s) - stacking , base pair , chemistry , base (topology) , sequence (biology) , degree (music) , dna , helix (gastropod) , linear regression , correlation , crystallography , combinatorics , stereochemistry , thermodynamics , physics , mathematics , statistics , geometry , mathematical analysis , biology , ecology , biochemistry , organic chemistry , snail , acoustics
T m values for 20 DNA duplexes with different repeating base sequences provided the data base for developing a rational and relatively simple methodology for computing apparent enthalpies for the helix → coil transitions of DNA helices, Δ H calc . The computational variables and their range of acceptable values were selected on the basis of physically plausible arguments. Over 350,000 different combinations of the variables were tested for degree of fit. It was therby possible to find a combination giving a high degree of linear fit between T m and Δ H calc (correlation coefficient, 0.99), with T m values deviating (on average) from the regression line by only ±2.17°C. Most of this uncertainty is attributed to experimental limitations, although computational approximations also contribute. With Δ H calc for the melting of each of the unique complementary dinucleotide fragments computed by the method developed, it is possible to estimate T m and (relative) Δ H calc reliable for the melting of any particular DNA [with base pairs G(I)·C and A·T] given only its base sequence. The Δ H calc values for the complementary dinucleotide fragments, together with statistical considerations, make it apparent that T m of DNAs with repeating base sequence show only an approximate linear dependence on G·C content because A·T and G·G pairs do not contribute to helix stability independently of the base‐pair sequence in which they occur. In fact, the nearestneighbor stacking interactions are so significant that certain complementary dinucleotide fragment sequences with 0,50, and 100% G·C content have the same stability.