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Molecular and Cellular Structure Determination


Module description

This module covers the application of state-of-the-art macromolecular crystallography and cryo-electron microscopy (EM) to the determination of three-dimensional structures important in molecular and cellular biology. The lectures and practicals will cover the basic principles of biological sample preparation, diffraction, imaging, data collection and structure determination by crystallography and cryo-EM for both molecular and cellular structures, along with structure validation and interpretation.

Indicative module syllabus

  • Introduction: principles of diffraction and imaging in biology, overview of biological structure determination, requirements for macromolecular crystallography (MX) and for cryo-electron microscopy (EM)
  • Macromolecular crystallography: the phase problem, molecular replacement
  • Modelling, refinement and validation in MX
  • Macromolecular structure determination by single particle EM
  • Cell tomography and interpretation of EM maps

Learning objectives

By the end of this module, you will be able to:

  • explain the principles of crystallography and electron microscopy as applied to biological material
  • describe the requirements for both molecular and cellular sample preparation for structure determination
  • explain the basics of diffraction, image processing and the principles of three-dimensional structure determination of macromolecular and cellular structures
  • give examples of the application of crystallography and EM in structural biology
  • evaluate the quality of structures determined by crystallography and EM.