SCIENCE

BioDesign's Software Advances Computer-Aided Molecular Design

California firm's Biograf packages are menu-driven, easy to use, and fully integrate graphics and molecular dynamics calculations

With computers of all shapes and sizes an integral part of the modern chemical laboratory, entrepreneurs are developing increasingly sophis­ticated methods for applying com­putational capabilities to the solu­tion of complex chemistry problems. One such group of methods has been labeled computer-aided mo­lecular design, or CAMD.

A handful of small companies have sprung up to offer CAMD packages. One such company is BioDesign Inc. of Pasadena, Calif.

According to Jeffrey R. Marusin, BioDesign vice president of mar­keting, the emergence of the CAMD market likely will follow a path analogous to the one followed by what has become known as CAD/ CAM (computer-aided design/com­puter-aided manufacturing), a mar­ket that has grown at about 30% per year for the past 10 years. Using similar projections, Marusin says, an­alysts peg the CAMD market at about $1 billion annually by 1995.

According to Marusin, the impe­tus for such strong growth can be found in the increasing competi­tion that exists in the pharmaceuti­cal and chemical industries. A vari­ety of factors have combined to cre­ate "real pressure to shorten the R&D cycle," he says. "CAMD offers a focused, scientifically based ap­proach to developing new materi­als" that can, at least in part, re­

place the time-consuming screen­ing techniques that traditionally have been used by chemists in their search for useful new compounds.

BioDesign was founded in 1984 by William A. Goddard III, chemis­try professor at California Institute of Technology; Barry D. Olafson; and Stephen L. Mayo. The compa­ny was self-financed. According to Marusin, BioDesign has been prof­itable for each of the past four years. The company is now shifting its focus somewhat from R&D to mar­keting the software products it has developed. BioDesign recently com­pleted a successful round of ven­ture capital financing.

BioDesign's primary product is a software package called Biograf, a sequence of programs designed for biological, chemical, and materials s imulat ions using the Evans & Sutherland PS300 family of three-

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Biograf software package predicted geometry (left photo) of inhibitor CLT, which is a dipeptide, (yellow) docked into active site of enzyme thermolysin; display of crystal structure (righ t photo) of Dickerson DNA dodecamer (blue and yellow strands) shows spine of hydration (orange)

24 February 1, 1988 C&EN

Goddard: polymer renaissance

^dimensional graphics terminals. The original Biograf package was de­signed to be run on Digital Equip­ment Corp/s VAX and MicroVAX computers. A subsequent package, Biograf/Sun, introduced in mid-1987, runs on the less-expensive Sun Microsystems Sun-3 and Sun-4 fam­ily of workstations, using either Sun's high-resolution graphics displays or the PS300 terminals. Biograf/Alliant runs on Alliant Computer's family of minisupercomputers.

Yet another package introduced in 1987, Biograf/GKS, supports a variety of graphics terminals that use the industry standard GKS graphics protocol. Biograf/GKS runs on the full line of DEC VAX com­puters, as well as on any desktop computer capable of support ing Tektronix emulation software, in­cluding IBM personal computers. Prices for the various Biograf pack­ages range from $34,950 to $95,000.

A key feature of Biograf that sep­arates it from other CAMD pack­ages, according to Goddard, who is BioDesign's chairman, is that the interactive graphical display and analysis are fully integrated with interactive or batch calculations of structure and dynamics. Other exist­ing CAMD packages, Goddard says, have been created by fusing sepa­rate graphics and molecular dynam­ics computer programs. That ap­proach prevents molecular dynam­

ics calculations from being fully interactive with the graphics aspects of the software, he maintains.

By contrast, Goddard says, inte­gration of the graphical display and energy calculations in Biograf great­ly facilitates, for example, the pre­diction of molecular structures or the results of docking interactions between molecules. Simulations can be done in real time and parame­ters modified on the basis of trends that develop as the simulation is being carried out.

The Biograf software is complete­ly menu driven, making it straight­forward to use. It can operate on molecular systems containing up to 20,000 atoms. In constructing mole­cules, Biograf offers general building capabilities using organic fragments, as well as specialized builders for peptides, DNA, lipids, carbohy­drates, and polymers. The program offers users a choice between Am­ber, Charmm, MM2, and BioDesign's Dreiding parameterized force fields for energy calculations.

Although Biograf, as its name implies, has been designed primar­ily for CAMD involving biological molecules, BioDesign intends to ad­dress "almost the entire range of chemical problems," according to Marusin. "That obviously involves more than just drug design. It in­cludes polymers, advanced materi­als, and crystals as well."

To that end, the company is in the final stages of developing soft­ware called Polygraf, which is simi­lar in design and capabilities to Biograf but oriented to the needs of polymer scientists. New synthet­ic methodologies that allow highly selective synthesis of polymers are ushering in a "renaissance in poly­mer science," Goddard says. To ex­ploit these synthetic techniques, however, scientists must be able to predict the properties of the poly­mers before they are synthesized, he points out. BioDesign has estab­lished a consortium of leading in­dustrial and academic polymer re­search scientists to stimulate the de­velopment of CAMD software for polymers, including Polygraf. Bio­Design also is working on CAMD software for modeling crystalline materials.

Rudy Baum, San Francisco

ΝAS, Soviet academy expand science links Scientific relations between the U.S. and U.S.S.R. are warming up, just as are political relations.

Last month, a delegation from the National Academy of Sciences visited the U.S.S.R. NAS president Frank Press and Soviet Academy of Sci­ences president Guriy I. Marchuk signed a five-year agreement that will expand and deepen scientific exchanges between the two acade­mies (C&EN, Jan. 18, page 21). At the same time, Samuel O. Thier, president of the Institute of Medi­cine (IOM), NAS's equivalent in the medical area, signed a five-year agreement in Moscow establishing for the first time scientific coopera­tion with the Soviet Academy of Medical Sciences. And other U.S. scientific groups and federal agen­cies are upgrading ties with Soviet scientists.

These increasing links restore re­lations drastically cut back in early 1980 by U.S. scientific organizations, individual scientists, and federal agencies in response to Soviet actions in Afghanistan and against Andrei Sakharov and other dissident scien­tists. NAS, for example, let its ex­change agreement with the Soviet academy expire in 1979, and did not renew it until 1986. NAS dropped

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Marchuk: tremendous advance

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