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Introduction to Structural Biology

Structural biology is an area of research concerned with the structure of biological molecules such as proteins and nucleic acids. These and other macromolecules are assembled into specific three-dimensional shapes in order to perform their particular functions. Structural biology aims to understand how these structures impact function at the atomic and molecular level, potentially affecting the chemical reactions that are central to all molecular and cellular functions.

Isothermal Titration Calorimetry (ITC) has become a key tool for studying structure/function activity relationships because of the high quality affinity and thermodynamic data that can be acquired in this simple to use and label-free technique. It has been shown that when binding is demonstrated by ITC there is a good correlation with the success of crystallization trials and ultimately good structural data. It is also used as a tool, together with Differential Scanning Calorimetry (DSC) and Dynamic Light Scattering (DLS) to reduce sample heterogeneity, critical in structural biology studies.

The Zetasizer Helix combines DLS with Raman spectroscopy to enable size measurements to be carried out simultaneously with a highly sensitive spectroscopic determination of a protein’s secondary and tertiary structure. This technique can be applied under standard formulation conditions to elucidate the molecular mechanisms driving many oligomerization, aggregation and agglomeration events or to provide complementary and supporting thermodynamic data to DSC.

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The use of ITC, DSC and thermodynamics in drug discovery and development:

How ITC can be used to reduce sample heterogeneity:

Binding studies using ITC:

MicroCal DSC Range:

The Zetasizer Helix: