What is the role of biophysical imaging in drug discovery?

Interested in our Spotlight on biophysical imaging? Check out this post with some key questions and answers you might need to help you navigate the field of biophysics in relation to drug discovery.

Jul 29, 2019
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What is biophysics?

Biophysics is an interdisciplinary approach that uses a combination of biochemical and chemical analytical techniques, spectroscopic techniques and computational methods to explore the relationship between physical properties and biological function. So, in a nutshell, biophysics seeks to use physics to explain the mechanisms that are at play (the structures, dynamics and interactions) to help biological systems function [1].

What do biophysics do?

Biophysics work in a range of fields – biology, physics, engineering and many more. They can help develop new and innovative technologies, aid drug-development programs and even practice law in fields like intellectual properties. As biophysics is such a wide and diverse discipline, biophysicist, as with any other kind of scientist, can end up working and applying their skills in a wide variety of places and ways [2].

Why is biophysics important?

The discoveries and developments of this field have and will continue to have an impact in some many areas. For example, did you know that the double helix structure of DNA was solved using a biophysical approach – x-ray crystallography [1]? With biophysics, it is possible to determine shape and structure of biological molecules and relationship to their function, which may not otherwise be possible without the use of these instruments and techniques.

What can biophysics do for drug discovery?

Biophysics offers researchers more information on the functions and mechanisms of our body; this extra information can then be used to assist our understanding of health and disease, which ultimately can be translated into the development of novel treatments.

It has shifted the focus of drug discovery and given researchers the ability to target more challenging molecules, explore the binding kinetics in therapeutic action and provide the foundation for fragment-based drug discovery [3]. Overall, it has given way to an alternative (and possibly more logical) approach to drug discovery, especially in the earlier stages [D], and as biophysical methods continue to rapidly develop, they will continue to transform drug discovery at all stages of the pipeline.

What is biophysical imaging?

These imaging techniques are an important aspect of biophysics. Without these tools researchers and scientists would not be able to obtain the structural information of the vast range of biological macromolecules.

What techniques are used in biophysical imaging?

Technique

Description 

X-ray crystallography

A technique used to obtain the 3D structure of molecules. By forming crystals of the molecules in question and measuring the angles and intensities of the x-ray beams diffracted into the crystal, researchers can determine the positions of all the atoms in the structure.

NMR Spectroscopy

A technique that provides highly detailed structural information by exploiting the magnetic properties of some atomic nuclei, to determine the physical and chemical properties of the atoms or molecules that contain them.

Mass spectrometry

An analytical technique that measures the mass-to-charge ratio of ions, to determine the chemical identity or structure of molecules.

Cryo-electron microscopy

A type of electron microscopy, in which the samples are cooled to cryogenic temperature before the electron beams are passes through the sample. It is often used to visualize and study large macromolecular complexes.

Circular dichroism spectroscopy

An absorption spectroscopy method that uses the difference in the absorption of left-handed and right-handed circularly polarized light to determine secondary structures of molecules.

Patch-clamp screening

This technique is used to study ion channel currents in isolated living cells, tissues or patches of cell membrane.

Confocal laser scanning microscopy

An optical imaging technique that captures 2D images of a sample at various depths, which can then be used to reconstruct the 3D image of the structure. 

Isothermal titration calorimetry

Used to characterize the thermodynamic parameters of interactions of compounds in a solution (for example between a target protein and ligand).

Thermal shift analysis

A method used to quantify the change in thermal denaturation temperature of a protein under a variety of conditions, such as pH, oxidation or the addition of a drug compound. It helps researchers determine optimal conditions for protein stabilization in solution.

Microscale thermophoresis

This technique detects changes in fluorescence, based on a change in the chemical microenvironment of the fluorescent probe, to determine the binding affinities between molecules.

Differential scanning calorimetry

A technique by which the difference in the amount of heat necessary to increase the temperature of a sample and reference; this is measured as a function of temperature.

Fluorescence microscopy

Combines the magnifying properties of light microscopy with the visualization of fluorescence to study the properties of both organic and inorganic substances.

Fluorescence spectroscopy

A method to analyze fluorescence from a sample, by using a beam of (ultraviolet) light to excite the electrons in molecules and causes them to emit light.

How can biophysical imaging techniques aid drug discovery?

These techniques have become a standard and essential part of drug discovery. From target identification in the earlier stages of the pipeline, to evaluation of disease models and characterization of compound binding, these methods can be implemented to provide necessary structural information.  For example, x-ray crystallography can be used to gain, at atomic resolution, the details of protein-ligand complexes, which is of use when determining how a protein and its binding partner interact to be able to create drugs that can target the same protein.

The continued evolution of these techniques and their application will aid the entire drug discovery pipeline to develop novel therapies for a variety of diseases.  


You can find out more about the research using biophysical imaging by checking out our Spotlight channel



Sources:

  1.  https://lsa.umich.edu/biophysics/about-us/what-is-biophysics.html
  2. https://www.biophysics.org/what-is-biophysics
  3. Renaud J-P, Chung C-W, Danielson U.H et al. Biophysics in drug discovery:  impact, challenges and opportunities. Nat. Rev. Drug Discov. 15, 679-698 (2019) 




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