NEWS OF THE WEEK PROTEIN
FOLDING
STRUCTURES BY COMPUTATION Software predicts structure and binding of membrane proteins CALCULATED
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TARTING W I T H N O T H I N G
but a string of amino acids, a new set of computer programs appears to be able to predict the structure and binding characteristics of membrane proteins. The ability to make such accurate predictions has been the goal of many scientists for decades, and it would be an enormous boon to a range of researchers, including drug designers and enzymologists. William A. Goddard III, director of the California Institute of Technology's Materials & Process Simulation Center, and colleagues report that the methods they've developed have predicted the pre-
Epinephrine nestles in predicted binding site of predicted human p i - a d r e n ergic receptor.
viously unknown structures of several important proteins [Proc. Nat. Acad. Sci. USA, 9 9 , 1 2 6 2 2 (2002)}. The proteins they chose to model, known as G-proteincoupled receptors, or GPCRs, are ubiquitous membrane proteins that play a role in processes such as vision, pain, allergies, and brain diseases. Molecules that bind to the proteins' receptors on the outside of the membrane activate so-called G p r o t e i n s on the o t h e r side, which in turn precipitate cascades of biological processes. But membrane proteins in general are so difficult to crystallize—they tend to denature in
BUSINESS
European Trio Sets Divestitures
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ignificant transactions at Bayer, Rhodia, and Lonza show that the European chemical industry is still in full restructuring mode. Bayer is selling its Rhein Chemie subsidiary, which makes rubber and plastics additives, to Boston-based investment firm Advent International for roughly $215 million. The business, based in Mannheim, Germany, has 1,100 employees worldwide and had sales last year of approximately $320 million. Bayer just completed the sale of another unwanted business, fragrance maker Haarmann & Reimer. For Rhodia, the Italian company Mossi & Ghisolfi is providing the opportunity to divest its holding in Brazil's Rhodia-ster. Mossi & Ghisolfi had agreed to buy Rhodia's 88.4% stake in the Brazilian company in July, but the changing economic situation in Brazil forced Rhodia to renegotiate the deal. Under the new agreement, Mossi & Ghisolfi
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will pay roughly $190 million for the business, South America's largest producer of polyester fiber and polyethylene terephthalate resins. It had sales of $337 million in 2001. Meanwhile, at Lonza, Chairman Martin Ebner has resigned after announcing that BZ Group Holding, a financial company he controls, will sell its 19.8% stake in Lonza. Former Lonza vice chairman Sergio Marchionne—now chief executive of the certification group Societe Generate de Surveillance—is to take over as nonexecutive chairman. Lonza is "not unhappy" with the change at the top, says one senior executive there, despite the temporary uncertainty about who might buy the shares. According to a company statement, the Lonza board will provide full details of its operational and strategic objectives to potential buyers of the stake, whether they be institutional investors or other specialties producers.—PATRICIA SHORT
aqueous solvents — that a 3-D X-ray structure exists for only one GPCR, bovine rhodopsin. In addition to bovine rhodopsin, Goddard's group studied a variety of GPCRs, including the human sweet receptor, the £adrenergic receptor, and mouse and rat olfactory receptors. The structure prediction program, called MembStruk, calculates the complex shape assumed by proteins, starting only from the amino acid sequence. T h e predicted bovine rhodopsin structure compares well with crystallographic data, the group reports. The protein structures for which no experimental data exist, however, were trickier to validate. Using a program they developed called HierDock, Goddard's group identified ligand binding sites on the proteins, then docked into them dozens of molecules for which binding data already exist. The predicted binding energies and conformations also agree well with the experimental data, particularly so with the (3-adrenergic receptor, they say The work "represents an outstanding contribution toward addressing the structure prediction and the function prediction of G-protein-coupled receptors," says Christodoulos A. Floudas, chemical engineering professor at Princeton University "If it applies generally to the prediction of other membrane proteins and other GPCRs, {this work} could have an enormous impact on pharmaceutical design, since many of the current blockbuster drugs interact with membrane proteins," says Ken A. Dill, professor of pharmaceutical chemistry at the University of California, San Francisco, an expert in computational protein structure prediction. Goddard tells C&EN, "I believe that we are at the point where the 20 years of struggling with protein-folding predictions are finally paying off."—ELIZABETH WILSON HTTP://PUBS.ACS.ORG/CEN
