|
PERFORMANCE
OF
COMPLETED
PROJECTS
STATUS REPORT
NUMBER 1
NIST SPECIAL PUBLICATION
950-1
Economic Assessment
Office
Advanced Technology Program
Gaithersburg, Maryland 20899
William F. Long
Business Performance Research Associates, Inc.
Bethesda, Maryland 20814
March 1999
CONTENTS
Acknowledgements
Executive Summary
Introduction
CHAPTER 1 - Overview of Completed Projects
Characteristics of the Projects
Timeline of Expected ATP Project
Activities and Impacts
Gains in Technical Knowledge
Dissemination of New Knowledge
Commercialization of the New Technology
Broad-Based Economic Benefits
CHAPTER 2 - Biotechnology
Aastrom Biosciences,
Inc.
Aphios Corporation
Molecular Simulations, Inc.
Thermo Trilogy Corporation
Tissue Engineering, Inc.
CHAPTER 3 - Chemicals and Chemical Processing
BioTraces, Inc.
CHAPTER 4 - Discrete Manufacturing
Auto Body Consortium (Joint
Venture)
HelpMate Robotics, Inc.
PreAmp Consortium (Joint Venture)
Saginaw Machine Systems, Inc.
CHAPTER 5 - Electronics
Accuwave Corporation
AstroPower, Inc.
Cree Research, Inc.
Cynosure, Inc.
Diamond Semiconductor Group, LLC
FSI International, Inc.
Galileo Corporation
Hampshire Instruments, Inc. (Joint Venture)
Illinois Superconductor Corporation
Light Age, Inc.
Lucent Technologies, Inc.
Multi-Film Venture (Joint Venture)
Nonvolatile Electronics, Inc.
Spire Corporation
Thomas Electronics, Inc.
CHAPTER 6 - Energy and Environment
American Superconductor Corporation
Armstrong World Industries, Inc.
E.I. duPont de Nemours & Company
Michigan Molecular Institute
CHAPTER 7 - Information, Computers, and Communications
Communication Intelligence Corporation #1
Communication Intelligence Corporation #2
Engineering Animation, Inc.
ETOM Technologies, Inc.
Mathematical Technologies, Inc.
Torrent Systems, Inc.
CHAPTER 8 - Materials
AlliedSignal, Inc.
Geltech Incorporated
IBM Corporation
APPENDICES
Appendix A: Development of New
Knowledge and Early Commercial Products and Processes
Appendix B: Terminated Projects
END NOTES
End Notes
Click here for PDF version of report.
Return to Main Page.
|
|
Molecular
Simulations, Inc.
(formerly Biosym Technologies, Inc.)
Powerful
Software for Designing New Molecules and Therapeutic Drugs
| The
traditional route to discovering new therapeutic drugs and other
useful chemicals should probably be called "semiautomated serendipity."
In the search for new drugs, hundreds of synthetic chemicals
and natural substances are put through a long series of trials,
starting with effectiveness tests in cell-based assays and concluding
with toxicity and effectiveness trials in laboratory animals
and, finally, humans. At each stage, the vast majority of substances
fail the test and are discarded. |
Using
Mathematics to Find New Drugs
This ATP project
with Molecular Simulations, Inc. (MSI), a small San Diego company
that had 170 employees when the project began, combined applied
mathematics and computer programming to develop new methods for
simulating molecular structures and reactions. The technology is
more efficient than conventional molecule-design techniques, a quality
that translates into speedier product development and lower costs.
The ATP-funded
effort led to new understanding of density functional theory (DFT),
a quantum mechanics method. Most work to understand molecules is
mathematical, and DFT is a relatively new form of applied mathematics
previously not widely used to simulate molecules. Researchers successfully
demonstrated the applicability of DFT to the study of biochemical
systems, the backbone of drug research, showing that DFT is as accurate
as other approaches and considerably less expensive.
The geometrical and electron structure of a siliceous
CHA-framework material isotopological with the mineral chabazine.
Zeolites and related crystalline microporous solids such as chabazite
have industrially useful separative and catalytic properties that
are determined by both the micropore architecture and the nature
of active sites.
Applications in New
Drugs and Petrochemicals
Prior to its
ATP award, MSI was already developing, marketing and supporting
a suite of software tools suitable for computing the behavior and
properties of molecules. The suite includes tools for bioinformatics,
combinatorial library optimization, determination of protein structures
from amino acid sequences, and structure- and analog-based rational
drug design. The ATP project enabled MSI researchers to incorporate
the new DFT knowledge into several of these tools. Most MSI software
users benefit from access to several different tools and will use
more than one of them in a given study.
One of the first
MSI tools to be enhanced with the DFT technology was Turbomole,
a computer software application that integrates a database of atomic
functions, a modern user-interface and mathematical tools like DFT.
The computer program calculates tables of molecular characteristics
and generates a three-dimensional structure of the molecule that
can be viewed by molecular graphics.
Another tool
upgraded with the new technology is DMol, a quantum chemistry program
that enables users to make reliable, quantitative predictions about
molecular systems. The ATP-funded technology-a DFT-based component
of the program-decreases the cost of these types of computation,
potentially reducing the cost of designing new molecules. The ATP-funded
technology is being used experimentally in petrochemical research,
and it has potential applications in biotechnology, rational drug
design, microelectronics and industrial fine chemicals research.
The geometry of a heme complex, optimized by first
principles density functional methods impleted in the program DMol,
using tehcnology developed under ATP sponsorship. In this molecule,
which contains more than 150 atoms, the central iron atom (central,
dark red) is coordinated by four nitrogen atoms (blue) of the heme
group, and a dioxygen molecule (red).
Benefits to Companies
and Consumers
Because the
MSI software is relatively low-cost, enters the discovery and development
cycle close to its beginning, and is used by research and development
personnel in large organizations, the benefits to the users of the
software can be large relative to what MSI earns through software
licenses. Such benefits will accrue to chemical, petrochemical,
pharmaceutical and biotechnology companies, as well as to companies
in other industries that use MSI software incorporating the ATP-funded
technology. Benefits will also accrue to people who use therapeutic
drugs and other products made by companies using the new technology.
In addition, scientists worldwide might benefit from a database
of molecular structures developed under the ATP award - MSI is considering
making the database available on the Internet.
MSI reports
that the ATP funds enabled it to complete research on the DFT technology
and incorporate the results into its software products some 18 months
earlier than it would otherwise have been able to do. The company,
its customers in the pharmaceutical and materials industries, and
their customers have all benefited. The project also facilitated
the dissemination of new knowledge, particularly via the many scientific
papers that were published about the ATP-funded technology.
Electron density isosurface of a zirconocene complex,
color-coded by electrostatic potential, as computed by the DMol
program. The geometrical and electronic structures in metallocene
complex govern the nature of the polyolefin products produced when
single site catalysts of this type are used to catalyze olefin polymerization.
Company Grows, Announces
IPO, is Acquired at a Large Premium
Since the end
of the ATP project in May 1995, the company has grown at a cumulative
annual rate of about 20 percent. In February 1997, it filed a Form
S1 with the Securities and Exchange Commission, announcing its intention
to conduct an Initial Public Offering of stock, and noted that it
expected to raise about $35 million by selling about half of the
stock in the company. In February 1998, the company and Pharmacopeia,
Inc., announced that Pharmacopeia would acquire MSI. The acquisition
was finalized in June 1998, in a transaction valued at approximately
$140 million.
PROJECT:
To develop density functional theory (DFT), a type of first
principles quantum mechanics, for use in the development of
new therapeutic drugs and other substances, an application that
is expected to achieve substantial time and cost savings.
Duration: 6/1/1992 - 5/31/1995
ATP number: 91-01-0224
FUNDING
(in thousands)::
| ATP |
$1,442 |
44% |
| Company |
1,867 |
56% |
| Total |
$3,309 |
|
ACCOMPLISHMENTS::
MSI successfully demonstrated the applicability of DFT to the
study of biochemical systems and developed software that employs
DFT to efficiently calculate molecular structures and energies.
The software was used to study biochemically relevant systems.
It proved as accurate as other approaches, yet much less expensive.
Also, the company
- prepared more
than 30 technical papers on the ATP-funded technology for
publication in professional journals or presentation at
conferences;
- implemented
a highly accurate way of applying DFT in the company's Turbomole
computer software product;
- expanded its
physical plant to accommodate larger R&D and production
facilities;
- was a finalist
for a Computerworld Smithsonian Award, the 1996 Innovator
Medal; and
- has grown at
a cumulative annual rate of about 20 percent since the end
of the ATP project in May 1995.
COMMERCIALIZATION
STATUS::
Commercialization is in progress. MSI incorporated the ATP-funded
technology into the company's existing Turbomole software package,
which has been distributed to more than 100 sites. The ATP-funded
technology has also been incorporated into MSI's quantum chemistry
workbench software. Benefits from the ATP-funded technology
are already accruing to users of MSI software, as well as to
users of products developed with the software.
OUTLOOK::
Expectations for this technology and the company are strong.
The technology has been incorporated into commercially distributed
products that are being used extensively by a relatively small,
yet global, community of scientists in academic, industrial
and governmental laboratories for rational drug design and petrochemical
research. It has potential applications in biotechnology, microelectronics
and industrial fine chemicals research.
COMPANY::
Molecular Simulations, Inc.
(MSI; formerly Biosym Technologies, Inc.)
9685 Scranton Road
San Diego, CA 92121
Contact:
John M. Newsam
Phone: (619) 546-5391
Number of employees:
170 at project start, 292 at the end of 1997
|
Return to Top
of Page
Go to other
sections of Chapter 2: BIOTECHNOLOGY
A Patient-Friendly Approach to Human Cell
Transplantation
Reducing Viral Contamination in Donated Blood
Powerful Software for Designing New Molecules and Therapeutic Drugs
Bioengineering of a Safe, Organic/Chemical
Insecticide
Prostheses Made of Biomaterials That Regenerate
Body Parts
Date created: March 1999
Last updated:
April 12, 2005
|
