Biomedical subjects

Alexander Spasic

Publications and source records attributed to Alexander Spasic.

4 recordsLinked to original sources

PubMed2005

Ion atmosphere of three-way junction nucleic acid.

The ion atmosphere of three-armed symmetric Y-shaped and asymmetric y-shaped A-RNA junctions in aqueous solution containing multivalent ions is described within the framework of a polyelectrolyte model. The fraction of "screening counterions" per polyion charge that shield the residual unneutralized charges from interacting with one another and the condensed counterions per polyion charge as a function of sodium and magnesium ion concentrations are determined. The predictions for the slope of log(k(o)/k(f)) as a function of Na+ and Mg2+ concentration, where k(o) and k(f) are the opening and folding rates of the three-helix junction molecule, respectively, are compared with experimental data (Kim et al. Proc. Nat. Acad. Sci. U.S.A. 2002, 96, 9077-9082).

Ions↗

PubMed2005

Compact and ordered collapse of randomly generated RNA sequences.

As the raw material for evolution, arbitrary RNA sequences represent the baseline for RNA structure formation and a standard to which evolved structures can be compared. Here, we set out to probe, using physical and chemical methods, the structural properties of RNAs having randomly generated oligonucleotide sequences that were of sufficient length and information content to encode complex, functional folds, yet were unbiased by either genealogical or functional constraints. Typically, these unevolved, nonfunctional RNAs had sequence-specific secondary structure configurations and compact magnesium-dependent conformational states comparable to those of evolved RNA isolates. But unlike evolved sequences, arbitrary sequences were prone to having multiple competing conformations. Thus, for RNAs the size of small ribozymes, natural selection seems necessary to achieve uniquely folding sequences, but not to account for the well-ordered secondary structures and overall compactness observed in nature.

Base Sequence↗

PubMed2004

Characteristics of migration patterns of DNA oligomers in gels and the relationship to the question of intrinsic DNA bending.

We have developed a methodology that is capable of quantitatively describing the electrophoretic mobility patterns of oligomeric B-DNA through polyacrylamide gels (PAG) in the presence of varying concentration of the organic solvent 2-methyl-2,4-pentanediol (MPD), used routinely to induce DNA crystallization. The model includes the ion atmosphere and its polarization, electrostatic excluded volume, hydrodynamic interactions, and fluctuation effects that characterize the overall size of the migrating polyion. Using this model, and by critically examining the mobility patterns of linear random-sequence B-DNA molecules in PAG as a function of MPD, we address the question of the discrepancy between current models used to explain the molecular origins of A-tract-induced DNA bending. Direct analysis of the mobility of B-DNA oligomers on PAG, and comparison to the mobility of A-tract-containing oligomers, shows a significant apparent effect of MPD on the mobility of generic B-DNA sequences, which is larger than the effect on A-tract-containing oligomers. The effect is chain-length dependent, especially at lower MPD concentration. Thus, the apparent reduction in gel mobility, as a function of MPD, is not unique to A-tract regions or A-tract-containing molecules. However, our analysis suggests that MPD molecules are probably excluded from the surface of both B-DNA and A-tract molecules. This is supported by circular dichroism studies on A-tract and B-DNA molecules in solutions containing various MPD concentrations.

Acrylic Resins↗

PubMed2003

Dynamics of curved DNA molecules: prediction and experiment.

We have developed a quantitative predictive model capable of describing the dynamics of migration of intrinsically curved DNA fragments on polyacrylamide gels. The model takes into account structural features of DNA, end-to-end distance, screening of hydrodynamic interactions, ionic strength of buffer, electrostatic persistence length, structural fluctuations of the macromolecule, counter condensation, and variation of dielectric constant and viscosity of water with MPD. In doing so, we have also addressed a decade old issue on the effect of the organic solvent 2-methyl-2,4-pentanediol on gel migration of phased A-tracts. We show here that A-tract-solvent interactions are less favored compared with A-tract-A-tract and solvent-solvent interactions.

DNA↗