Z. Foldespapp et al., FRACTAL DIMENSION OF ERROR SEQUENCE DYNAMICS IN QUANTITATIVE MODELINGOF SYNTHESES OF SHORT OLIGONUCLEOTIDE AND SINGLE-STRANDED-DNA SEQUENCES, Journal of theoretical biology, 174(4), 1995, pp. 391-408
Oligonucleotides are becoming more and more important in molecular bio
medicine; for example, they are used as defined primers in polymerase
chain reaction and as antisense oligonucleotides in gene therapy. In t
his paper, we model the dynamics of polymer-supported oligonucleotide
synthesis to an inverse power law of driven multi-cycle synthesis on f
ixed starting sites. The mathematical model is employed by presenting
the accompanying view of error sequences dynamics. This model is a pra
ctical one, and is applicable beyond oligonucleotide synthesis to dyna
mics of biological diversity. Computer simulations show that the polym
er support synthesis of oligonucleotides and single-stranded DNA seque
nces in iterated cyclic format can be assumed as scale-invariant. This
synthesis is quantitatively described by nonlinear equations. From th
ese the fractal dimension D-u (N, d) is derived as the growth term (N
= number of target nucleotides, d = coupling probability function). D-
u (N, d) is directly measurable from oligonucleotide yields via high-p
erformance liquid chromatography or capillary electrophoresis, and qua
ntitative gel electrophoresis. Different oligonucleotide syntheses, in
cluding those with large-scale products can be directly compared with
regard to error sequences dynamics. In addition, for short sequences t
he fractal dimension D-u (N, d) is characteristic for the efficiency w
ith which a polymer support of a given load allows oligonucleotide cha
in growth. We analyze the results of separations of crude oligonucleot
ide product from the synthesis of a 30 mer. Preliminary analysis of a
238 mer single-stranded DNA sequence is consistent with a simulated es
timate of crude synthesis product, although the target sequence itself
is not detectable. We characterize the oligonucleotide support synthe
ses by simulated and experimentally determined values of the fractal d
imension D-u (N, d(o)) within imitations (d(o) = constant (average) co
upling probability).