Modeling Molecules
Thanks to the space program, scientists are modeling molecules
with the goal of effectively discovering new treatments for diseases.
NASA's Goddard Space Flight Center, along with other government
organizations, provided Small Business Innovation Research
(SBIR) funding for technology that could simulate spacecraft,
vehicle, and machine dynamics, as well as biomechanical motions.
This SBIR project spunoff into the development of software that
can model the dynamics of molecules. Moldyn, Inc., of Cambridge,
Massachusetts, patented a technology that can simulate low-frequency
molecular motions and properties, such as movements among a molecule's
constituent parts.
This commercially available modeling method is known as Multibody
Order (N) Dynamics (MBO(N)D). In MBO(N)D, a molecule is substructured
into a set of interconnected rigid and flexible bodies. Substructuring
organizes groups of similarly behaving atoms into interacting
flexible bodies. These flexible bodies replace the computational
burden of mapping each individual atom. MBO(N)D reduces the number
of calculations from tens of thousands of atoms to a few hundred,
or less, bodies. Conventional atom-by-atom molecular dynamics
can require weeks, sometimes months, to simulate the behavior
of a few molecules. Moldyn's multibody approach cuts the computational
time by up to a hundredfold, while also yielding comparable accuracy
with all-atom methods.
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Pharmaceutical companies
are using the method for a variety of molecular analyses, including
realistic modeling of drug/protein interactions. |
Moldyn's MBO(N)D technology is available as Insight II 97.0
from Molecular Simulations, Inc. The software is an accelerator
for molecular dynamics that uses the same mathematical algorithms
originally developed for large flexible satellites to reach time
and size scales that were not attainable through conventional
methods. In the aerospace industry, the method is used to account
for forces on hundreds of thousands of parts in spacecraft and
satellites.
Pharmaceutical companies are using the method for a variety
of molecular analyses, including realistic modeling of drug/protein
interactions and comparison of these interactions with others
found in vast databases. Drug companies use databases containing
hundreds of thousands to millions of different molecules and
molecule fragments to look for potential medicines. The MBO(N)D
software allows efficient screening of these large databases
to find molecules that can "dock" successfully with
the active sites of proteins. The result of this innovation is
faster, less expensive drug development than what is allowed
by conventional atom-by-atom computational methods.
Drug discovery has changed over the past two decades to include
the study of significant structural components in and around
the cell. Molecular structures of proteins and receptor-ligand
complexes play an important role in the discovery of pharmaceutical
agents. A ligand is a biological compound that fits a receptor
within or on the cell surface. This fitting is analogous to a
lock-and-key arrangement. Drugs that mimic the shape of a natural
ligand can be used to regulate a signal in order to manipulate
a therapeutic interaction between the synthetic ligand and the
cell.
A major breakthrough with this development is to permit the
solution of realistic-sized molecular dynamics problems on a
moderate workstation, rather than on supercomputers.
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