Single-molecule platform for drug discovery: methods and apparatuses for drug discovery, including discovery of anticancer and antiviral agents

Inventors

Goel, Anita

Assignees

Nanobiosym Inc

Abstract

One aspect of the invention provides a system for drug discovery, drug development, drug screening, or drug validation. The system includes: a sample chamber comprising a target protein and a drug candidate that may interfere with the target protein in the sample chamber, wherein the sample chamber is configured to: detect one or more of the following: (a) interference between the drug candidate the target protein and/or (b) one or more dynamics of the drug candidate on the target protein, wherein the one or more dynamics comprise affinity of the drug candidate to the target protein, and select the drug candidate if one or more desirable dynamics is detected. The system includes one or more immobilized surfaces and is configured to detect interactions between the drug candidate and the target protein at the single-molecule level.

Core Innovation

The invention provides a system for drug discovery, drug development, drug screening, or drug validation that uses single-molecule manipulation and measurement of nucleic-acid interaction with a target protein in the presence of a drug candidate. A sample chamber contains a target protein, a nucleic acid that interacts with the target protein, and a drug candidate that may interfere with the target protein.

A measurement mechanism manipulates the nucleic acid and is controlled to maintain a constant tension on the nucleic acid during interaction with the target protein. The system measures a time-dependent signal representing the interaction and defines the signal as a mechanical signature of the interaction, enabling real-time observation of interaction dynamics such as template-related mechanical behavior and polymerase-related mechanical signatures.

The computing device compares the measured time-dependent signal to a baseline signal for the interaction between the nucleic acid and the target protein to determine whether the interaction is modified by the drug candidate. The approach supports screening and validation by identifying whether drug candidates modify, inhibit, or interfere with enzyme activity through differences from baseline mechanical signatures, including signatures tied to polymerization velocity and termination states.

Claims Coverage

The provided independent claim content includes three inventive features. The core features are maintaining constant tension on the nucleic acid, measuring a time-dependent interaction signal, and comparing the measured signal to a baseline signal to determine whether the drug candidate modifies the interaction.

Across the provided claim content, drug-candidate determination is based on measuring a time-dependent interaction signal from a nucleic-acid/target-protein system under constant tension, then comparing that signal to a baseline interaction signal to determine whether the drug candidate modifies the interaction.

Stated Advantages

Documented Applications