CHAPTER 2 The Chemistry of Living Things

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• Old school antisense
• New schoolRNA interference

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• RNA interference

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NIH-NLM 2003
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Protein Structure
Imaging Experimental X-ray diffraction
data Predicting structure in silico from sequence
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Experimental structures in the Protein Data Bank
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• Determining Structures-Structural Proteomics
• Figure 6.10 Rational Approach

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• Aquaporin as an example Fig 6.11
• How to prevent H30 entry?
• Homotetramer 3A, Water is 2.8 A

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HIV reverse transcriptase
Structure is Function

• DNA (human genome)
• RNA (HIV virus)
• Protein

Goodsell, PDB
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Goodsell, PDB
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Figure 17.0 Ribosome
Structural Predictions just from raw protein
sequence?
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Figure 17.0 Ribosome
1 ggcacgaggc acggctgtgc aggcacgcat gcaggccagc .
1 atctgcacgt ggttatgctg ccggagtttg ggccgccact.
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CASPCommunity Wide Assessment of techniques for
Protein Structure Prediction
An example

• Every two years, contest to test protein
  structure prediction from primary sequence

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• Structure Based or Rational
• Drug Design
• One nice trick use crystallization Fig 6.12

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• Detecting the Proteome Directly
• 2-D Gels Figure 6.18-21

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• Limitations
• Detection
• Quantification
• Identification
• Reproducibility

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• MS/MS Figure 6.19-6.20

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• MS/MS Figure 6.19-6.20

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• The Problem of Quantitation
• Figure 6.24 Direct Abundance detection
• Figure 6.25 Phospholation