Abstract: Disclosed are methods for analyzing molecular binding events in which the formation of ligand/antiligand complexes can be directly detected in a mixture without requiring separation of the components of the mixture from each other by measuring bulk properties of the mixture (i.e., properties that have contributions from several or all of the components present in the mixture). Using these techniques, it is possible to screen libraries without labeling either the target antiligand or ligand. The invention also provides a method for determining the strength of ligand/antiligand binding by further analysis of the same signals.

Abstract: A sample container for minimizing evaporation of a contained volume of sample includes a container housing, a repuncturable self-sealing membrane, and a collapsible sample bag. The container housing includes an open end and a hollow interior region. The repuncturable self-sealing membrane configured to self-seal after repeated punctures is engaged in the open end of the container housing and includes an exterior surface exposed to the external environment and an interior surface oriented toward the hollow interior region of the container housing. The collapsible sample bag includes a proximate end that is permanently attached to the interior surface of the repuncturable self-sealing membrane.

Abstract: The present invention provides methods and compositions for detection of compounds that have activity in modulating activity of membrane-spanning, signal-transducing (MSST) proteins, e.g., agonists, and antagonists. The detection method is based upon detection of a conformational change in a MSST protein upon interaction with a ligand. Conformational change of the MSST protein upon ligand interaction is accomplished by modifying the MSST protein to comprise a conformationally sensitive detectable probe, so that ligand interaction that results in a conformational change in the MSST protein is detected by a change in detectable signal from the detectable probe. The conformationally sensitive detectable probe can be a chemical label (e.g., a fluorophore) or moiety integral to the protein (e.g., a protease cleavage site, or immunodetectable moiety). The conformational assays of the invention provide for high-throughput screening.

Abstract: Disclosed are methods for analyzing molecular binding events in which the formation of ligand/antiligand complexes can be directly detected in a mixture without requiring separation of the components of the mixture from each other by measuring bulk properties of the mixture (i.e., properties that have contributions from several or all of the components present in the mixture). Using these techniques, it is possible to screen libraries without labeling either the target antiligand or ligand. The invention also provides a method for determining the strength of ligand/antiligand binding by further analysis of the same signals.

Abstract: The present invention provides methods and compositions for detection of compounds that have activity in modulating G protein-coupled receptor (GPCR) activity, e.g., agonists, and antagonists. The detection method is based upon detection of a conformational change in a GPCR upon interaction with a ligand. Conformational change of the GPCR upon ligand interaction can be accomplished by modifying the GPCR to have a bound detectable label so that ligand interaction results in a conformational change in the GPCR that is detected by a change in detectable signal from the detectable label. Conformational change of the GPCR upon ligand interaction can also be detected by detecting a change in the accessibility of a protease cleavage site to protease cleavage, where the protease cleavage site is naturally-occurring in the GPCR or introduced into the GPCR.