Measuring molecules to improve drug design

February 5, 2009
Measuring molecules to improve drug design
Fluorescence microscopy image of 100nm microspheres used to develop the DAC microscopy method for measuring molecules. Image: CSIRO

(PhysOrg.com) -- CSIRO has patented an improved microscopy method for measuring the shapes and sizes of proteins which could help scientists create new pharmaceuticals that are a better match for the proteins they target.

The method, called Differential Aberration Correction (DAC) microscopy, measures distances at the molecular level in two and three dimensions using conventional fluorescence microscopy.

A special feature of the new method, written up recently in the Journal of Microscopy, is that it allows scientists to measure proteins in solution, which is how they exist in nature, instead of using coated or crystallised proteins as other techniques do. This is particularly important for rational drug design but has broader life sciences applications.

The leader of CSIRO’s Biotech Imaging team, Dr Pascal Vallotton, says DAC microscopy measures distances a million times smaller than a tape measure can - in nanometres rather than millimetres. One nanometre is one billionth of a metre.

“Just as a tailor measures up a person for a suit, we want to use our technique to measure accurate dimensions of proteins called membrane receptors,” Dr Vallotton says.

“These proteins sit on cell boundaries, acting as gate-keepers, and they represent a class of biomolecules targetted by over 50 per cent of pharmaceuticals.

“Understanding the complex structures of these molecules and how new drugs affect their structure will help drug companies design more effective pharmaceuticals.”

Cells are often viewed using conventional fluorescence microscopy. However, images obtained this way are inaccurate because light is bent differently for different wavelengths through the microscope. Several universities have attempted complex and onerous hardware-based solutions to try to fix this problem.

CSIRO researchers instead used a software-based approach that precisely corrects the distortion at every point in the image.

DAC microscopy is an improvement on an older technology, called FRET, which can measure distances from 1-10 nanometres. DAC can measure 1-250 nanometres, giving a more complete picture of drug-membrane receptor interactions. It will complement other techniques like X-ray crystallography.

The DAC software was tested using fluorescent polystyrene microspheres only 100 nm across - about one thousandth the width of a hair.

“We are currently looking at more samples that require the ability to see single molecules with very high contrast. Results are extremely encouraging and we are starting to explore commercial possibilities,” Dr Vallotton says.

The DAC software was recently demonstrated in the US and will be presented at the Society for Biomolecular Screening conference in Lilles, France in April.

Provided by CSIRO

Explore further: Researchers develop new monomer fluorescent protein for SR imaging

Related Stories

Picoscale precision though ultrathin film piezoelectricity

August 10, 2016

Piezoelectricity (aka the piezoelectric effect) occurs within certain materials – crystals (notably quartz), some ceramics, bone, DNA, and a number of proteins – when the application of mechanical stress or vibration ...

Nanoribbons in solutions mimic nature

August 15, 2016

Graphene nanoribbons (GNRs) bend and twist easily in solution, making them adaptable for biological uses like DNA analysis, drug delivery and biomimetic applications, according to scientists at Rice University.

Watching molecular machines at work

August 12, 2016

When one cell divides into two - that is how all forms of life are propagated - the newly born daughter cells have to be equipped with everything they will need in their tiny lives. Most important of all is that they inherit ...

Discovery could help treatments for sickle cell disease

August 8, 2016

An interdisciplinary, international group of researchers has found new biophysical markers that could help improve the understanding of treatments for sickle cell disease, a step toward developing better methods for treating ...

Recommended for you

Quest to find the 'missing physics' at play in landslides

August 30, 2016

During the 1990s, Charles S. Campbell, now a professor in the Department of Aerospace and Mechanical Engineering at the University of Southern California, began exploring why large landslides flow great distances with apparently ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.