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Global Phasing Puts Research Goals First as it Augments Structure Determination Consortium

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In the relatively obscure world of x-ray crystallography software development, it seems one company has decided to go out of its way to create a low profile. Global Phasing, an eight-person x-ray crystallography software developer based in Cambridge, UK, doesn’t have much of a website—just a portal for members of its research consortium—and in contrast to other companies developing bioinformatics tools, doesn’t make too much of a fuss about itself.

“The research agenda is the driving force [of the company],” said founder Gerard Bricogne, a protein crystallographer formerly at the UK’s Medical Research Council’s Laboratory of Molecular Biology in Cambridge. “The purpose is to get a certain amount of work done.”

Last week, however, Global Phasing had some news to tell. The company signed on Cambridge -based drug developer Astex Technology to its research consortium, and is currently wrapping up agreements with the 15 or so pharmaceutical and biotechnology companies that fund the company’s research.

Bricogne said that “all the big pharmas” are members of the consortium—meaning they fund Global Phasing’s research in return for early access to the software—because the tools the company provides help researchers solve protein structures using x-ray crystallography data that would otherwise be of too poor quality to use.

“Often crystals do not diffract as one would wish, and they’re not amenable to being solved [using] fairly widespread software,” said Bricogne. “What we write gives either better quality [results] or results that would otherwise have been unobtainable.”

To do this, Bricogne and his team have developed two programs, called Sharp and Buster, that use statistical methods such as Bayesian inferene, among others, to draw more information from the experimental x-ray data. The Sharp software helps calculate the correct phases for the x-ray data, and Buster uses that information to help complete and refine the crystal structure.

During the first three-year “phase” of its research contract with its consortium members, Bricogne and his team focused on developing the phasing and refinement software. Now, Global Phasing hopes to integrate all the mathematical analysis of x-ray data into one software program, a project Bricogne has proposed for the next three years of research.

“We want to go towards a greater degree of integration and automation of the whole structure determination process, from the raw data acquisition to the structure refinement,” he said. In addition, Bricogne said he hopes to build software that can access databases of protein structures, a capability that will help researchers better phase and refine protein structures.

Members of the Global Phasing consortium have access to beta versions of the company’s software, Bricogne said, and receive training and customer support from Global Phasing scientists. Members also participate in the group’s annual meetings to discuss research priorities.

Bricogne, however, remains reticent about who the members are; an would not disclose the amount of funding he receives from them or global phasing’s revenues.

Bricogne is happy with this. “My company is not a publicity-seeking startup fixated on market-related figures,” he said. “We’re a company whose activities are indistinguishable from those of a research group.”

— JSM

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