Biodesy, Inc.

Quanta Therapeutics, Inc.

Bluelight Therapeutics, Inc.

Joshua S Salafsky

Dar Bahatt

Louis John Dietz

Ray Hebert

Ryan P McGuinness

Carl Benton Moree, Iii

Methods and devices for identifying agents that block binding or activation of peripheral membrane proteins are disclosed.

Methods and devices for detection of peripheral membrane protein interactions using nonlinear optical techniques

Methods are disclosed for tethering a biological entity to a substrate comprising: (a) forming a supported lipid bilayer on a surface of a substrate, wherein the supported lipid bilayer comprises an anchor molecule conjugated to a first affinity tag that is present in the lipid bilayer at a concentration greater than or equal to 5 mole percent; and (b) contacting the supported lipid bilayer with a biological entity, wherein the biological entity comprises an nonlinear-active label and a second affinity tag capable of binding to the first affinity tag, thereby tethering the biological entity to the supported lipid bilayer in an oriented fashion.

Attachment of proteins to interfaces for use in nonlinear optical detection

Methods, devices, and systems are disclosed for determining protein structure and dynamics using second harmonic generation (SHG) and related surface-selective nonlinear optical techniques.

Methods for determining protein structure using a surface-selective nonlinear optical technique

Methods, devices, and systems are disclosed for performing high throughput analysis of conformational change in biological molecules or other biological entities using surface-selective nonlinear optical detection techniques.

Systems and methods for high throughput analysis of conformation in biological entities

Provided herein are compositions and methods for identifying and detecting modulators of Ras protein conformational states through the use of second harmonic generation (SHG) technology. Also provided herein are methods for detecting a conformational changes in the three dimensional structure of a protein bound to a supported lipid bilayer.

Methods for identifying modulators of Ras using nonlinear techniques

A system for making molecules, and proteins in particular, suitable for detection by a surface-selective nonlinear optical technique. A first use of the invention is for determining a protein's structure in real space and real time. A second use of the invention is to detect a protein or its activity (conformational change). A third use of the invention is for drug screening. A further aspect of the present invention is measuring probe tilt angle orientation in an oriented protein.

Nonlinear optical detection of molecules comprising an unnatural amino acid possessing a hyperpolarizability

A method is disclosed for classifying and distinguishing between type I and type II kinase inhibitors. The method involves the use of non-linear optical techniques, in particular second-harmonic generation (SHG) to identify conformational changes in kinase proteins obtained from known type I or type II inhibitors. The method further involves deducing the manner of binding of unknown inhibitors by comparison with the signal changes produced by known ligands. The method is also applied to comparing the conformational changes induced by the binding of generic and branded kinase inhibitor drugs to a target kinase.

Classification of kinase inhibitors using nonlinear optical techniques

The present invention discloses, inter alia, methods for labeling a target protein with an SHG-active probe for detection by second harmonic or sum-frequency generation in order to identify agents which bind to an allosteric site on the target protein thereby altering its structural conformation.

Methods for detecting allosteric modulators of protein

A nonlinear optical technique, such as second or third harmonic or sum or difference frequency generation, is used to detect binding interactions, or the degree or extent of binding, that comprise conformational change. In one aspect of the present invention, the nonlinear optical technique detects a conformational change in a probe due to target binding. In another aspect of the invention, the nonlinear optical technique screens candidate probes by detecting a conformational change due to a probe-target interaction. In another aspect of the invention, the nonlinear optical technique screens candidate modulators of a probe-target interaction by detecting a conformational change in the presence of the modulator.

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South San Francisco, CA, United States of America

Joshua S Salafsky