New tools help identify the most promising protein molecules for drug development

A state-of-the-art digital tool that makes it cheaper, safer, and faster for pharmaceutical companies to predict protein stability-an important step in the development of new drugs-is unfolded through a spinout by scientists at the University of Bath in the United Kingdom. The company that has been, BLOC Lab.

Launched this week, this tool will help researchers identify the most promising protein molecules for drug development. It can play an important role in the production of monoclonal antibodies (mAbs). The market for these therapeutic antibodies is worth over £ 70 billion.

Monoclonal antibodies are a type of protein that is derived from natural antibodies and is purified and mass-produced in the laboratory. They are steadily changing the way we treat and prevent diseases, from conditions that affect the cancer and immune system to viral infections. The coronavirus pandemic has generated special interest in mAbs, as many protein candidates have high promise as a treatment for Covid-19 and are currently being tested in humans.

Stability is the key

Only mAbs that are known to be stable (that is, they do not easily decompose or aggregate to form toxic compounds) are suitable for development, and finding a stable candidate costs the cost of finding a new drug. Time will increase significantly.

In the past, the process of determining protein stability has been a major headache for pharmaceutical companies, with researchers testing a vast library of molecules to look for medicinal proteins. However, a tool developed at Bath (called Quantitative Understanding of Biomolecular Edge Shifts (QUBES)) can predict protein stability with incredible speed and accuracy.

QUBES is very excited about the potential of QUBES as it is ready to use for quality assurance, prescribing and development in the biopharmacy industry. “

Dr. Chris Padney, Developer of QUBES, Department of Biology and Biochemistry, University of Bath

“It is well known that proteins are unstable for good reason. The body wants to recycle them constantly. But therapeutic agents need stability. When proteins break down and aggregate. Finding a stable protein is a pharmaceutical company, but using our tools to find the best possible molecule can save you a lot of development time and cost. “

QUBES fingerprint

QUBES works by allowing researchers to accurately “fingerprint” the structure of proteins and predict their stability under almost any concentration or formulation condition. This technique uses fluorescence to map the structure of a protein and applies mathematical algorithms based on the position and type of atoms in the protein to calculate stability. Thanks to an online suite of software, also developed in Bath, labs can interpret fluorescence data from anywhere in the world using the equipment found in most biochemical labs without modification.

Dr. Padney elaborated on fingerprinting technology: “Proteins contain tryptophan, a fluorescent amino acid. Every protein molecule has a unique fluorescent signature, and QUBES takes advantage of this optical phenomenon. Then apply mathematical techniques to analyze and interpret the fluorescence.

“The software suite takes this academic work and makes it incredibly easy for people to use. It can be run on any mobile phone or any machine. It’s super fast, very easy and incredible. It offers a modest level of security.-In fact, we usually have a grade of security reserved for the financial services industry. “

What sets QUBES apart from its competitors is its read quality and its extremely high flexibility. Dr. Padney explains: “Our approach is not only faster, more accurate and more sensitive than any other tool on the market, but unlike other tools on the market that require set conditions, at any concentration and in any formulation. Can predict the stability of “”

Dr. Padney’s team recently conducted a validation study of QUBES technology with the National Institute of Physical Sciences (NPL) under a government-sponsored “measurement of recovery scheme” scheme that provides independent verification of technology by major national analytical facilities. It was conducted.

Dr. Alex Jones, who led the study at NPL, said: “We tested the QUBES approach using a variety of analytical methods and found that it was able to track subtle changes in protein structure and stability with amazing sensitivity compared to established methods. The approach is fast. Easy to implement. “