"MultiSeq (pronounced multi-seek) allows you to bring in both
structure and sequences without structure, and use the complementary
information contained within them to investigate changes in the
system," said Zaida Luthey-Schulten, a professor of
chemistry and a
researcher at the Beckman
Institute for Advanced Science and Technology at the University
of Illinois. "By placing bioinformatics in the context of evolution,
we can also perform comparative dynamics studies of proteins from
different domains of life."
Currently, more than 3 million
sequences and 35,000 structures of proteins and nucleic acids are
available for study. By providing an environment for the
evolutionary analysis of this data, the software can help scientists
gain valuable insight into basic scientific questions, such as the
origin of life, as well as questions of a more practical nature,
such as the development of resistance to ribosome-targeting
Developed by Luthey-Schulten and graduate students Elijah
Roberts, John Eargle and Dan Wright, MultiSeq is a major extension
of the Multiple Alignment tool that is provided as part of Visual
Molecular Dynamics, a program for visualizing and analyzing
molecular dynamics simulations. Developed at the U of I and
distributed free of charge, the VMD program is designed to
efficiently handle large three-dimensional systems containing more
than a million atoms.
MultiSeq extends VMD's capabilities by incorporating the more
diverse evolutionary data available in sequences into the analysis
For example, the computational tools in MultiSeq may help
scientists understand the evolution of ribosomes, the basic
machinery of translation. Translation is a key component of all
life, and the components of this cellular machinery are the
biomolecules with the most linear line of descent.
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"If we want to try and understand how translation has changed among
the three domains of life, we have to at least be able to overlap
and compare three ribosomes," Luthey-Schulten said. "Last year, we
could not compare two ribosomes. Now, using MultiSeq, we can compare
more than 20 ribosomes."
MultiSeq combines both sequence and
structure data within an evolutionary framework, using information
science to organize and search the data, information visualization
to assist in recognizing correlations, mathematics to formulate
statistical inferences, and biology to analyze chemical and physical
properties in terms of sequence and structure changes.
The researchers developed MultiSeq in collaboration with the
Theoretical and Computational
Biophysics group at the Beckman Institute, and with the National
Institutes of Health Resource for Macromolecular Modeling and
Bioinformatics. They describe the software in a paper accepted for
publication in the journal BMC Bioinformatics and featured
the journal. The software is being used in classrooms this fall as a
teaching tool for computational chemical biology.
"We believe the complexity present in biology cannot be fully
understood without using evolution as an underlying framework," the
researchers write. "This approach can speed up research by revealing
unproductive tasks in advance or by exposing new paths through the
introduction of distant but related data."
Funding was provided by the National Science Foundation, the U.S.
Department of Energy and the National Institutes of Health. For
details on how to download and use the software, visit the MultiSeq
of Illinois news release]