CSMB

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Center for Structural Molecular Biology

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The Center for Structural Molecular Biology at ORNL is dedicated to developing instrumentation and methods for determining the 3-dimensional structures of proteins, nucleic acids (DNA/RNA) and their higher order complexes. The tools of the CSMB will help understand how these macromolecular systems are formed and how they interact with other systems in living cells. The focus of the CSMB is to bridge the information gap between cellular function and the molecular mechanisms that drive it. The suite of tools being developed by the CSMB includes:

  • Bio-SANS, a Small-Angle Neutron Scattering (SANS) facility for biological samples, has been completed at the ORNL High-Flux Isotope Reactor (HFIR). The CSMB is also closely aligned with researchers at the Spallation Neutron Source (SNS).
  • Isotope Labeling Laboratories for cloning, gene expression, purification and characterization of labeled biological macromolecules are planned; our Bio-Deuteration Lab is currently operational and accepting proposals.
  • Computational Techniques have been developed for the study of macromolecular complexes by SANS. Combined with selective Deuterium-labeling, it is now possible to develop detailed structural models that will enable the understanding of function.

Another computation technique developed for the study of calculates solution small-angle X-ray and neutron scattering intensity profiles by ORNL-SAS. This makes it possible to develop from a wide variety of structures, including atomicresolution models of proteins and protein complexes, low-resolution models defined in any manner, or combinations of both.

Neutron diffraction, spectroscopy and scattering are excellent tools for studying biological systems because neutrons interact differently with hydrogen and its isotope deuterium. As a result, it is possible to:

  • pinpoint individual hydrogen positions in proteins
  • probe the structure and dynamics of proteins, nucleic acids and membranes
  • characterize higher order complexes

These studies use neutrons to address questions that have not - or cannot - be answered by other techniques.

SANS can be used to study biological systems under near physiological conditions, providing insight into interactions within complexes and conformational changes in response to stimuli. Through the use of specific deuterium labeling SANS makes it possible to highlight and map components within larger complexes (e.g. viruses, ribosome). The SANS instruments at ORNL's High Flux Isotope Reactor and Spallation Neutron Source will open new opportunities for studying conformational changes and molecular processes on biologically relevant timescales.

The CSMB welcomes interest from researchers from a wide variety of scientific disciplines including Physics, Chemistry, Biology, Biochemistry, Molecular Biology and Computational Sciences.

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