‘Shapeshifting’ computer programme will open up drug discovery for tricky disease targets

Computer technology that opens up the discovery of smarter drugs to treat major illnesses including heart disease has been invented by scientists at the University of Strathclyde.

The Shapeshifting Inspired Discovery (SID) programme decodes the structures of proteins in our cells that scientists suspect may hold the key to new treatments. The programme can rapidly analyse the complicated shapes and identify how the proteins might be 'shapeshifted' by drugs.

Shapeshifting involves a different and more subtle mechanism than conventional drugs, which stop the proteins working completely. The team behind SID – developed at Strathclyde over the last decade and now being deployed in collaboration with US firm Serometrix – will apply it to drug discovery for a range of diseases.

Mark Dufton of Strathclyde’s Department of Pure and Applied Chemistry, said: 'Conventional drug discovery is extremely expensive, time consuming and often heavily reliant on ‘lottery techniques’ to identify useful drugs by chance.

'While this has certainly reaped benefits before, these traditional methods are becoming less fruitful and many new drug candidates found in this way are being abandoned because of toxicity problems and side effects. Drugs that act by shapeshifting work in a much smarter way that is a closer mimic of natural mechanisms for control.

'The ability of SID to predict the scope for ‘shapeshifting’ enables us to probe large, complex biological molecules – which have evolved their intricate shapes over hundreds of millions of years – so that we can analyse where and whether they can be targeted to provide treatments. When targeting is more selective, and the mechanism is smarter, a new generation of better medicines beckons.

The ability of SID to predict the scope for ‘shapeshifting’ enables us to probe large, complex biological molecules

'Diseases are often caused by certain molecules in the body being either too active or not active enough – or by them operating in the wrong place at the wrong time. The new technology helps discovery of ‘shapeshifting’ drugs that can carefully adjust these biological molecules, bringing them under control and thus less likely to cause problems.

'We can use this knowledge, in the case of a specific disease, to help a key protein be more or less active when the system is not working optimally on its own.'

John Wilson, of Strathclyde’s Department of Computer and Information Sciences, added that the SID algorithm provides a near real-time, 3D graphical output that makes it easy for clients quickly to understand where to focus their efforts.

Serometrix's Chief Executive Mike Muehlemann said SID is already yielding promising early leads in the search for potential treatments for high cholesterol and cardiovascular disease.

'With this combination of technologies we expect to reduce the number of early trial compounds from millions to hundreds, potentially shaving years off the discovery-development programme,' he said.

'Even though regulatory costs may remain high, or escalate, an increased yield has the potential for significant cost reduction in the resulting pharmaceuticals.'