Case study

Software for crystallography supporting new drug development

Crystallographic software developed at York has underpinned the design of many pharmaceutical products.

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The issue

The pharmaceutical industry is an important sector in the UK, generating huge economic and health benefits.

The largest aspect of the sector is drug development. In the first half of 2018 alone, new drugs for migraines (Erenumab), ovarian cancer (Niraparib) and Alzheimers (Aducanamab) were introduced.

Developing these drugs requires structural studies using crystallographic software.

The research

York Structural Biology Laboratory (YSBL) has pioneered the development of portable general purpose software for protein structure solution, where previously crystallographic studies often required custom software development. The Laboratory embodies a tradition of linking computational method developers with working crystallographers, leading to practical and useful tools for the whole community.

YSBL has developed many world-leading crystallographic software applications. In particular, the COOT graphical model building and validation software is typically cited in around ten new research papers each day, and was cited in around 95 per cent of papers citing a major graphical model-building tool during 2014.

A significant factor in the success of COOT is the work which has gone into making best-of-class model-building, refinement and validation tools available to the non-specialist user, as well as a powerful interactive fitting tool. Recent developments include a growing library of tools for locating and modelling ligands – of particular relevance to pharmaceutical users, as well as support for electron microscopy data.

The REFMAC software for structural refinement, another YSBL development, is a key component of the widely used CCP4 software for macromolecular x-ray crystallography. REFMAC was used in the refinement of 60 per cent of structures deposited to the PDB between 2008 and 2011. It has since been adapted to the refinement of electron microscopy structures.

The outcome

YSBL's software output has had major commercial success. The CCP4 suite that YSBL contributes to yields over £1m in commercial user fees annually, with clients including GSK as well as various smaller businesses in the pharmaceutical and biotechnology sectors.

More significant economic impact is derived from YSBL's research through the capabilities the software creates within global organisations. Drug discovery underpinned by use of the software has a financial impact in excess of £100m a year.

Featured researcher
Kevin Cowtan

Kevin Cowtan

Professor Cowtan's expertise includes automated protein structure solution and climate science.

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Featured researcher
Jon Agirre

Jon Agirre

Dr Agirre's research focuses on computational methods in structural glycobiology.

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Featured researcher
Keith Wilson

Keith Wilson

Professor Wilson examines the relationship between structure and function in biologically active macromolecules using the techniques of protein crystallography.

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