Impact of computers on chemistry examined
Toronto Stephen C. Stinson, New York
How computers have affected industrial and academic chemical research, chemical education, and chemical information management is a question explored over four days of sessions sponsored by the Computer Secretariat. Actually, said George Levy of Syracuse University, chemists today see only the impact of computer technology that is three or more years old. Levy, who is both science and technology professor and director of the Computer Applications & Software Engineering (CASE) Center at Syracuse, said that this year's graphics supercomputers provide chemists with a link from computer to eye to mind. At last, chemists can perform fast, three-dimensional rotations of high molecular weight molecules whose atoms are rendered as space-filling, shaded spheres. They can also show solvation effects and "dock" molecules together to test for fits of drug candidates with receptors. Indeed, Levy's audience could ride the escalator one floor up from the room where he spoke to the exposition hall and watch computers doing these things. Although the high data-transmission speeds of graphics supercomputers bypass the slow speeds of today's networks. Levy said that wide-area networks definitely have a future. Though today's Ethernet transmits 300 kilobytes per second at 10 MHz, newer systems to appear in two to three years will transmit more than 100 megabytes (MB) per second at 100 MHz. These high speeds, coupled with hardware and software advances, will enable chemists to view results in one place while computation occurs at a distant location, and the links and gateways among components of the system will seem invisible. Computers of the future will be
more powerful owing to use of reduced instruction set computing (RISC), algorithm-specific integrated circuits, and many central processors in parallel. Small computers will have thousands and large computers 1 million parallel chips. In fact, Levy called parallelization in programing the challenge of the next 10 years. Among languages, FORTRAN 77 dominates individual persons' programing, whereas C is becoming standard for commercial projects. This is because C is both closely related to machine languages for faster-running programs and bound up with the UNIX operating system, w h i c h is well a d a p t e d to networking. Levy finds it interesting that Pascal, popular in the early 1980s, is rapidly fading from the research and commercial scene. In a later presentation, however, computer science professor G. Scott Owen of Georgia State University said that Pascal is the language of choice in educational programing. The computer has certainly affected industrial chemical research, and Peter M. Smith of S. C. Johnson & Co. and Philip D. Kutzenco of American Cyanamid described these effects. But although the two
agreed on the deep penetration of industrial research departments by computers, each gave slightly different views on implications for the future. Kutzenco, who is group leader for research computer systems at Cyanamid's Stamford, Conn., technical center, drew a bright picture of his management's enthusiastic support in terms of hardware, software, and courses in applications. But Smith, who is group leader for research information services at the Racine, Wis., consumer products company, cautioned that computers and their support are overhead expenses within research, which is itself an overhead activity. Smith estimated that penetration of computers into industrial research is about 50%. As he put it, "This means a tube in every second cube." Moreover, control of research computer systems usually lies with that department. And the technical and experimental orientation of research means that chemists need less support than do other groups within the company. Typically, only 3% of the research staff is involved with computer support. Databases of molecular structures, chemical reactions, and journal articles have also changed literature
On Sun workstation, deconvolution of two-dimensional oligonucleotide spectra took 20 minutes;graphics supercomputer would cut time to two minutes June 27, 1988 C&EN
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Science
For chemists, computer systems offer diverse applications First chemists could hear how computers have affected the practice of their science in sessions of the Computer Secretariat at the Toronto Convention Centre, then they could ride the escalator from the meeting room to the upstairs exposition hall and watch it happen. It almost seemed that every second booth was that of a computer manufacturer or software company. The most arresting display was the array of 25 television screens mounted by Ardent Computer, Sunnyvale, Calif., that played the firm's musical show highlighting the capabilities of its graphics computer (C&EN, June 20, page 84). Ardent had teamed with BioDesign, Pasadena, Calif., to adapt BioDesign's Biograf and Polygraf molecular modeling programs to run at ultrahigh speeds on Ardent's Titan graphics supercomputer. Ardent introduced the resulting system, called the Molecular Simulator, in Toronto. Molecular modeling allows chemists to enter structures of molecules into a computer, whose program does molecular mechanics (effective force field) calculations to display the most likely conformation, complete with cor-
searches profoundly, Kutzenco noted. Where chemists once trekked to the library to thumb through many and incomplete printed sources, none newer than months or years old, they now turn to their own desktops to call up a few more complete and current sources, often whole texts as well as abstracts. Gone are the times when chemists had to know the name of a compound or reaction type, could only search compound by compound, and had to devise means of cross-referencing. The new databases are structure-dependent, enabling searches by molecular and reaction substructures, with cross-references showing up automatically. Molecular modeling, so much in evidence in the exposition hall, has replaced chemists' intuitive ideas based on inspection of passive balland-stick models. Predictions of conformation and reactivity now come from computations on dynamic, moving models. 32
June 27, 1988 C&EN
rect bond angles and distances and, if desired, space filling. Molecular mechanics calculations use x-ray crystallographic data, infrared spectroscopic force constants, and heats of formation of known compounds to predict conformations of unknown structures. The Ardent is a 64-bit computer that uses one to four processors in parallel to execute 16 million instructions per second (MIPS) and 16 million floating point operations per second (Mflops) per processor. Such speeds result from inclusion of control, computational, and graphics units plus instruction and data memories in the same processor, with processors linked to one another and to main memory by a bus capable of transmitting 256 megabytes (MB) per second. The price for a system with one processor plus Ardent's own graphics software and either Biograf or Polygraf is $130,000. With two processors, the price is $165,000. The company is still working to develop systems with three and four processors. Also included is a version of the UNIX operating system for communications and networking, Fortran and C
Kutzenco outlined Cyanamid's modern computer network at Stamford with mini- and microcomputers and workstations mutually interlinked. The firm provides courses in computer literacy, applicationsspecific courses, and personal assistance from computer scientists. For the future, he said, the situation can only improve as chemists, themselves becoming more computer literate, get access to more powerful hardware and software, with new sources appearing on compact disks and development of a common interface for chemical representation. But many chemists will have to justify these improvements to management to move into such a bright future, said Smith of S. C. Johnson. He pointed out that if 500 chemists save one hour a week by being more useful, this is a productivity increase of 2.5%, worth $1 million per year. But this does not translate into $1 million cash in hand. Moreover, advances in software
compilers, and the Ardent's Doré graphics program. The compilers adapt programs written for Cray and VAX computers to parallel processing. BioDesign's Biograf is optimized for biological chemistry. Though chemists can use it to cobble together any organic molecule, there is a library of amino acids, nucleotides, and carbohydrate structures that allows rapid assembly of peptides, nucleic acids, carbohydrates, and lipids. Polygraf is optimized for rapid assembly of polymers from a library of monomers. Each program interacts with molecular mechanics programs such as MM2 or structure databases like MACCS. In BioDesign's own booth in Toronto, the company demonstrated adaptation of these programs to an FX/40 computer from Alliant Computer Systems Corp., Littleton, Mass. This 64-bit machine does parallel computing with one to four processors linked to one another and to main memory by buses of capacity 188 MB per second. Speeds are 94.4 Mflops with all four processors. The operating system is a variant of UNIX. Compilers are available that accept programs in Fortran, C, and Ada and adapt them to parallel processing.
and decreasing costs of computing power do not mean that improved systems cost less. This is because programs that are more powerful and easier to use cost more and require more computing power. But Smith suggested that chemists can overcome these problems. They must demonstrate actual benefits to management rather than simply give measurements of improved capabilities. "This concern will fade," he said, "when there is a MacCray on every desk." "Computers have not affected chemical education as much as they should have nor as much as they will in the future," said Owen of Georgia State. Indeed, his own career pointed up one barrier to progress. Originally educated as a chemist, Owen said that colleagues on the chemistry faculty looked askance at his work on chemical education programing. They thought it wasn't chemistry. It was only when he
transferred to the computer science department that his efforts were appreciated as scholarship. A second barrier to progress has been the combination of rapidly changing microcomputer technology with limited high school and university budgets. Owen traced the evolution from the Apple II of 1977 through the IBM PC and the PC/ AT to today's machines based on the 80386 microprocessor. These changes meant not only outlays for computers but also for the new software they required. Owen predicted that the situation will ease in the 1990s with the appearance of an advanced machine as a stable platform from which chemical educators can work. Such a machine will have five to 10 microprocessors, 8 to 32 MB of random-access memory, 400 MB of read-only memory on a compact disk, a 100- to 300-M hard disk, a 1024-by-780-pixel monitor, and 256-by-256-MB graphics, all for $2000. For the present, Owen said that computers are not much used for class demonstrations because of long set-up times and lack of software and projection systems. Likewise there is little use to control experiments except through simple game ports. More ambitious interfaces would need costly analog-digital interconvertersand software. Actual uses are programing instruction, word processing, drill and practice, simulations (titrations, molecular motion, nuclear magnetic resonance, and high-performance liquid chromatography), and computationally intensive activities (molecular orbital and molecular mechanics calculations). Programs used include spreadsheets in the public domain as templates for experimental design and data entry. But overall, Owen said, there has been little effect of computers on how people actually teach chemistry. He ascribed this to lack of faculty interest and to emphasis on technology rather than pedagogy. He called for interdisciplinary efforts among chemistry instructors, cognitive psychologists, and computer scientists to generate the chemical educational progress of the future. •
Scope of ICP/MS expands to many fields
Toronto Although scarcely more than 10 years old, inductively coupled plasma-mass spectrometry (ICP/MS) is one of the fastest-growing analytical techniques. The method, which combines the power of the ICP for atomizing and ionizing samples with the sensitivity and selectivity of mass spectrometric detection, is finding application in more and more fields. At a symposium on ICP/MS, Robert S. Houk of Iowa State University—one of the pioneers in the field—provided an overview of the present capabilities and future prospects of the method. He notes, for example, that detection limits currently are in the range of 10 to 100 ng per L for most elements. Among other common analytical techniques, only electrothermal atomic absorption spectrometry, a single-element technique, offers comparable low detection limits. "ICP/MS has made multielement determinations possible at concentrations that could be measured previously only for one element at a time," Houk says. "The improved detection limits alone have spurred numerous applications in areas such as environmental sciences, geochemistry, and the nuclear industry. ICP/ MS is probably the best technique available for determination of trace rare-earth mixtures." ICP/MS is also notable for its ability to measure isotope ratios rapidly. "This facilitates elemental determinations by isotope dilution and isotope tracer studies of elemental fates and pathways in biological and environmental systems," Houk observes. For example, he says, one can trace the sources of lead in environmental samples because the natural variation of lead isotope ratios is enough to be detected, and ICP/MS is sensitive enough to do so. Along that line, Houk notes that that ability has been extended to the measurement of potassium iso-
tope ratios by recent "chemical modifications to the ICP" that eliminate interferences from Ar+ and ArH + ions. The general approach may be useful for other isotopic determinations as well. Regarding future prospects, Houk notes that ICP/MS can be used as an element- and isotope-selective detector for gas or liquid chromatography. Thus, different chemical species (of selenium or arsenic, for example) can be separated chromatographically, with the ICP/MS monitoring the Se or As in each form. The detection limits for this combined technique are good enough to consider its use for speciation measurements of levels of elemental species present in actual biological or environmental samples, Houk asserts. "Although there has been a lot of research on other techniques for such speciation measurements, these have in general not demonstrated sufficient powers of detection for real applications on a widespread basis," he adds. ICP/MS is a relatively youthful technique, Houk says, so there is substantial room for improvement in many of its figures of merit. Precision should be improved both for elemental determinations and isotope ratio measurements. For example, "many more biological tracer experiments and possibly even some geochemical chronology studies could be done if the precision of
Houk: detection limits spur uses June 27, 1988 C&EN
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