Dynamics of DNA Breathing and Folding for Molecular Recognition and Computation

This thesis is centered on the development of the molecular beacon, as a new DNA probe for DNA genotyping, D N A computation and biophysical studies of DNA conformations. Molecular beacons are single-stranded DNA molecules that form a stem-and-loop structure. A fluorophore and a quencher are grafted at their two ends to report their conformations: when the molecular beacon is closed, fluorophore and quencher are held in close proximity and the fluorescence is quenched; when the molecular beacon is open, fluorophore and quencher are far apart, and the fluorescence is restored. Molecular beacons are ideal DNA probes coupling conformational switch with fluorescence signal turning-ON. We use molecular beacons to study the molecular recognition of single-stranded DNA (ssDNA) oligonucleotide. We present a thermodynamic diagram to show that structural constraints make the molecular beacon highly sensitive to the presence of mismatches in its target. We introduce a sequence sensitivity parameter to quantitatively compare different DNA probes, and propose an algorithm to optimally tune the probe\u27s structure for enhanced sequence discrimination. Logic gates (OR and AND gates) using molecular beacons are designed to carry most elementary molecular computations. The conformational changes associated with such computations can be used to concatenate many chemical reactions, and carry out complex molecular computations. Molecular beacons are also ideal probes to study DNA secondary structures and their fluctuations. We develop the fluorescence correlation spectroscopy (FCS) technique to monitor the dynamics of relaxation of DNA conformational fluctuations. We first measure the opening and closing timescales of DNA hairpin-loops. Activation barriers for opening and closing for different loop lengths and sequences are analyzed to better account for the stability of DNA secondary structures. A sequence dependent rigidity of ssDNA has been discovered, and analyzed in terms of base stacking. We then use F C S to study the dynamics of double-stranded DNA (dsDNA) breathing modes with synthetic DNA constructs. The analysis of the base pairing fluctuation dynamics, monitored by fluorescence, unravels lifetimes of breathing modes ranging from 1/us to 1ms. Long-range distortions of the d s DNA have been unraveled for purine-rich sequences, of relevance to the specificity of transcription initiation in prokaryotes

Remote Sensing of Earth Resources: A literature survey with indexes (1970 - 1973 supplement). Section 1: Abstracts

Abstracts of reports, articles, and other documents introduced into the NASA scientific and technical information system between March 1970 and December 1973 are presented in the following areas: agriculture and forestry, environmental changes and cultural resources, geodesy and cartography, geology and mineral resources, oceanography and marine resources, hydrology and water management, data processing and distribution systems, instrumentation and sensors, and economic analysis