Week 6

• Gene expression is the process by which information from a gene is used to produce a functional product, such as a protein

  
• Gene expression can be divided into two main steps: transcription (copying gene information into mRNA) and translation (using mRNA to build a protein)
• Transcription is the process of copying the information from a gene into a messenger RNA (mRNA) molecule
• Translation is the process of using the information in the mRNA to build a protein
• Proteomics involves systematic high-throughput separation to characterize proteins within biological systems
• Disease processes become manifest at the protein level, with protein expression differing in normal and diseased tissues, aiding in identifying targets for drug discovery
• Bioinformatics involves methods/tools to transform raw sequence data into meaningful information and compare genomes across organisms or diseased states
• Bioinformatics is used to map out specific patterns of dysregulation in diseased vs non-diseased states and can model infection dynamics and predict disease outbreaks
• Structural Biology involves the study of biomolecular structures in 2D and 3D representations
• Structural Biology helps understand biomolecule function, reaction mechanisms, ligand binding, and physiological roles
• Proteins with quaternary structures are made up of multiple polypeptide chains, known as subunits
• A domain is an independently folded region of a protein with a specific function, while a motif is a conserved amino acid sequence characterizing a biochemical function
• Changes in protein conformation can occur due to protein-protein or protein-ligand binding, alterations in physiological conditions like pH or temperature, and mutations impacting protein structure and function
• Protein cavities allow for the binding of substrates or drug molecules, with orthosteric sites being functional sites like active sites for enzymes, and allosteric sites affecting protein function away from the orthosteric site
• The allosteric site of a protein is explored for the development of modulators or drugs with increased specificity or to overcome resistance
• Determining biomolecular structures involves techniques like X-ray diffraction and cryo-electron microscopy to visualize and understand the 3D structures of biological molecules
• Gene expression involves two main steps: transcription (copying gene information into mRNA) and translation (using mRNA to build a protein)
• 1. ray crystallography:

  • Determines about 80% of currently available protein structures
  • Requires high protein concentration and crystallization
  • Able to trace amino acid side chains
  • No molecular weight limit
  • Common method for drug design
• Nuclear Magnetic Resonance (NMR):

  • Size limit of 350 amino acids (40kDa)
  • Does not require crystallization
  • Measures nuclear magnetism or NM changes in a molecule
  • NMR spectroscopy measures the absorption of light due to changes in nuclear spin orientation
• Cryo-Electron Microscopy (Cryo-EM):

  • Used for high-resolution 3D imaging
  • Samples studied in native states
  • Suitable for membrane proteins
  • No destruction of samples due to low dose parameters