Study protein conformational changes in real-time at the single-molecule level

Part of: Drug Research

Study protein conformational changes in real-time at the single-molecule level

Scientists can use optical tweezers to trap beads and catch a protein in between. The folding and unfolding of the protein can then be monitored by moving the beads while measuring the force and extension. The combination of optical tweezers with simultaneous multicolor fluorescence measurements allows correlation of the global mechanical properties of the protein with the local structural properties.

The C-Trap™ Optical Tweezers – Fluorescence Microscopy system provides the ability to apply and measure force and extension of a protein target while simultaneously obtaining the fluorescence signals from e.g. FRET fluorophores. This allows one to identify the (in)active and intermediate states and resolve the interaction energies of proteins. All these together provide important insights into the protein’s functional mechanism. Because of the C-Trap’s unique microfluidics system, this can be done under different experimental conditions: in the presence or absence of (ant)agonists, co-factors and/or pharmaceuticals, within the same experiment.

Figure 1 shows the obtained equilibrium dynamics trace of calmodulin – a calcium-binding protein. The graph reveals that calmodulin switches between two major states, an open and a closed one, without a clear preference. We can resolve intermediate steps as calmodulin occasionally jumps to a third state for short periods of time.

C-Trap protein conformational dynamics drug discovery

1 Full-length CaM protein at 10 mM Ca2+ showing equilibrium dynamics between multiple states, represented by the dashed grey lines. Data is recorded at 50 kHz (grey line) and averaged at 200 Hz (red line). The histogram quantifies the most populated states in the inset (right panel) showing two peaks at 6.5 ± 0.1 pN and 7.8 ± 0.09 pN (mean ± standard deviation).

Sample courtesy of Prof. Carlos Bustamante at the University of California, Berkeley.
Peltz et al. (2016) Nature Communications
Lamichhane et al. (2015) PNAS
Gupta et al. (2015) Nature Communications


C-Trap® Optical Tweezers Fluorescence & Label-free Microscopy

Optical Tweezers and Fluorescence Microscopy

The C-Trap is the world’s first instrument that allows simultaneous manipulation and visualization of molecular interactions in real-time. It combines high-resolution optical tweezers, confocal microscopy or STED nanoscopy with an advanced microfluidics system in a truly integrated and correlated solution.

M-Trap® Optical Tweezers Fluorescence & Label-free Microscopy

Optical Tweezers

The m-Trap is the first entry-level optical tweezers instrument specifically developed for high-resolution single-molecule research. Ultra-high force resolution and stability, with incredible throughput, ease of use and modularity ‒ all at an unprecedented price level.

Key Product FeaturesC-Trap®m-Trap®
Conformational changes and states
Force-induced structural transitions
Visualization of ligand interactions using fluorescence
Investigation of higher order structures using FRET
Rapid buffer exchange for fast experimental workflow

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