Protecting our warfighters? Yes, there is an app for that.
To provide our troops with enhanced countermeasure protections,
it is imperative that defense agencies develop cost-effective
products that allow for faster lab-to-battlefield application. One
effort underway, funded by the Defense Threat Reduction Agency’s
Chemical and Biological Technologies Department, is developing an
app that enables researchers to expedite countermeasure studies.
CANDO has a convenient web browser/Jupyter notebook interface that
allows computational chemists to write programs to construct
molecules. It also supports graphical tools for visualizing and
drawing molecules. CANDO incorporates a software distribution
framework that will allow chemists to develop and distribute
applications for designing molecules. (Image courtesy of Christian
Schafmeister, Ph.D., Temple University - December 12, 2017)
Natural proteins used for research are expensive, fragile and
inefficient. As such, researchers are increasingly turning to
biomimetics — human made substances that imitate natural ones.
However, until now, there has not been a quick or easy way to design
biomimetics for a specific function.
An effort by Temple
University’s Christian Schafmeister, Ph.D., has resulted in a
modeling app that changes that. Computer-Aided Nanostructure Design
and Optimization (CANDO) provides scientists the capability to
rationally design biomimetics, similar to how microcircuits,
software and machines are designed. The app performs conformational
analysis on molecules constructed from non-natural building blocks,
searches molecules for substructures, automatically assigns atom
types, identifies rings, carries out conformational searching and
automatically determines stereochemistry.
builds conformational databases of these building blocks to further
enable the creation of improved biomimetics. Using the web
browser-based Jupyter notebook interface, CANDO allows chemists to
write software that assembles chemical structures into new
molecules. In addition, the app allows researchers to construct 3-D
coordinates of the resulting molecules, sketches molecules, build
3-D structures, visualize them within the browser and prepare them
for sophisticated simulations. CANDO implements a programming
environment where chemistry apps can be written and deployed through
an internet-based package manager for open use.
used CANDO to create a stable metallo-enzyme that mimics proteins to
accelerate organophosphonate rearrangements. These biomimetics are
composed of a central scaffold that can be modified with various
functional groups in order to create the perfect pocket where
catalytic activity can happen. Called “spiroligomers,” these
biomimetics have extraordinary utility because they form
well-defined, predictable molecular shapes that can be readily
modified and customized. These can be assembled to build
controllable, tunable enzymes.
Adversaries continue to use
and synthesize new threats. Mother Nature has had little time to
evolve proteins to thwart known threat agents and no time to defeat
synthesized ones. Advances in computational biomimetic design
present a unique opportunity to pursue rational design and synthesis
of small molecules that can effectively respond to current threats
and be rapidly engineered to address emerging ones for the next
generation of countermeasures to safeguard our warfighters.
By Catherine Keaty, Ph.D. - Defense Threat Reduction Agency CBTD
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