摘要:
This invention relates to a method of identifying a difference between at least two data sets made up of ordered elements utilizing internal features within the data sets for calculations relating to normalization, scaling, and difference finding.
摘要:
This invention includes methods for analyzing data generated by various solid-state NMR experiments, including rotational echo double resonance (REDOR), transferred echo double resonance (TEDOR), dipolar recoupling at the magic angle (DRAMA), dipolar recoupling with a windowless sequence (DRAWS), and melding of spin-locking and DRAMA (MELODRAMA). The methods are based alternately on a new analytical transform or the maximum entropy method and their multidimensional extensions. They permit simultaneous, multiple distance measurements of high accuracy and precision, even from nuclei with identical chemical shifts. By providing high quality easily obtained distance measurement from disordered solid state materials, this invention also improves drug discovery and design through fast determination of structures of pharmaceutical lead compounds, drug molecules, or their targets.
摘要:
In a specific embodiment, this invention comprises a method for selecting highly targeted lead compounds for design of a drug that binds to a target molecule. The method comprises screening a diversity library against the target molecule of interest to pick the selectively binding members. Next the structure of the selected members is examined and a candidate pharmacophore responsible for the binding to the target molecule is determined. Next, preferably by REDOR nuclear magnetic resonance, several highly accurate interatomic distances are determined in certain of the selected members which are related to the candidate pharmacophore. A highly accurate consensus, configurational bias, Monte Carlo method determination of the structure of the candidate pharmacophore is made using the structure of the selected members and incorporating as constraints the shared selected members and incorporating as constraints the shared candidate phamacophore and the several measured distances. This determination is adapted to efficiently examine only relatively low energy configurations while respecting any structural constraints present in the organic diversity library. If the diversity library contains short peptides, the determination respects the known degrees of freedom of peptides as well as any internal constraints, such as those imposed by disulfide bridges. Finally, the highly accurate pharmacophore so determined is used to select lead organics for drug development targeted at the initial target molecule.
摘要:
This invention relates to a method and device for separating particles according to their diffusivities in a separation medium by means of a spatially and temporally varying electric potential. The method takes advantage of the transport of charged particles subject to an electric potential that is cycled between an off-state (in which the potential is flat) and one or more on-states, in which the potential is preferably spatially periodic with a plurality of eccentrically shaped stationary wells. The potential wells are at a constant spatial positions in the on-state. Differences in liquid-phase diffusivities lead to charged particle separation. A separation medium fills physically defined separation lanes (15) in the device. Electrodes deposited substantially transverse to the lanes create the required potential. Advantageously, injection ports (16) allow sample loading, and special gating electrodes focus the sample prior to separation.
摘要:
This invention is an integrated instrument for the high capacity electrophoretic analysis of biopolymer samples. It comprises a specialized high-voltage, electrophoretic module in which migration lanes are formed between a bottom plate (446) and a plurality of etched grooves in a top plate (438), the module permitting concurrent separation of 80 or more separate samples. In thermal contact with the bottom plate (446) is a thermal control module incorporating a plurality of Peltier heat transfer devices for the control of temperature and gradients in the electrophoretic medium. Fragments are detected by a transmission imaging spectrograph which simultaneously spatially focuses and spectrally resolves the detection region of all the migration lanes. The spectrograph comprises a transmission dispersion element and a CCD array to detect signals. Signal analysis comprises the steps of noise filtering, comparison in a configuration space with signal prototypes, and selection of the best prototype. Optionally post-processing is done by a Monte-Carlo simulated annealing algorithm to improve results. Optionally, an array of micro-reactors can be integrated into the instrument for the generation of sequencing reaction fragments directly from crude DNA samples.
摘要:
A device for separating charged particles comprising: an upper substate (11); a lower substrate (12); separation lanes (15) defined on the upper substrate, a first plurality of electrodes (21, 22...); a first pad (18), said first plurality of electrodes connected to said first pad (13); a second plurality of electrodes (21, 23...); a second pad (14), said second plurality of electrodes connected to said second pad; said pads and electrodes deposited on the lower substrate; and said first plurality of electrodes and said second plurality of electrodes are interdigitated. During the operation of the device, charged particles are subjected to an electric potential that is cycled between an off-state and one or more on states, in which the potential is preferably spatially periodic with a plurality of eccentrically shaped stationary potential wells.