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2013 Cottrell Scholars Collaborative New Faculty Workshops in Chemistry Exploring Watson-Crick Base Pairing and DNA Structure Learning Goals – Content Knowledge 1) Explore how hydrogen bond donors and acceptors of the nucleosides(tides) influences the overall double helical structure of DNA including isosteric nature of the W-C basepairs and groove structure. 2) Predict the impact of a non-W-C pairing on a DNA double helix? Find evidence to support or refute your initial prediction by using the models provided. 3) Explore how the groove structure of a double helix might allow a protein to “read” a DNA sequence without having to unwind the DNA duplex. Learning Goals – Skills Development • Use models to visualize biomolecular structures • Transition between structural scales (atomic/macromolecular) • Recognize links between atomic functionality and macromolecular properties/behavior The common nucleosides H H N HO N N N H N O N N HO H N N N O O H OH OH deoxyguanosine deoxyadenosine H H O N H N N N HO N HO O O O O OH OH deoxythymidine deoxycytidine Use the nucleotides to explore the Watson-Crick base pairing patterns. - Compare the distance between pairs of carbon atoms (C1’-C1’ or C4’-C4’)? Are they equidistant for A•U and G•C base pairs? 0 1 2 3 4 5 6 7 8 1 Cottrell Scholars Collaborative New Faculty Workshops in Chemistry 2013 What properties of the nucleotides give rise to the structure of B-form DNA? Sequence specific read out occurs in the grooves of duplex DNA 2 2013 Cottrell Scholars Collaborative New Faculty Workshops in Chemistry Reading the sequence of DNA without unfolding the duplex Use the models of the AT and GC base-pairs above to consider the potential interaction surface in the major and minor grooves of the following DNA sequences: (↑ = donor; ↓ = H-bond acceptor; ∅ - CH3 steric interaction; O - H atom) EcoRI binding site Major Groove 5 3 G C A BamHI binding site Minor Groove 3 5 Major Groove 3 5 G C T G A T A T T A C G G C T A A T T 5 3 Minor Groove 3 5 G C C G C A T A T A T A T A T A C G C G C G C G C G 5 3 5 3 3 5 Reading the sequence of DNA without unfolding the duplex Use the models of the AT and GC base-pairs above to consider the potential interaction surface in the major and minor grooves of the following DNA sequences: (↑ = donor; ↓ = H-bond acceptor; ∅ - CH3 steric interaction; O - H atom) EcoRI binding site Major Groove 5 3 G ↓ ↓! ↑ O C BamHI binding site Minor Groove 3 5 G ↓! ↑ ↓! C Major Groove 3 5 G ↓ ↓! ↑ O C Minor Groove 3 5 G ↓! ↑ ↓! C A ↓! ↑ ↓! ∅ T A ↓! O ↓! T G ↓ ↓! ↑ O C G ↓! ↑ ↓! C A ↓! ↑ ↓! ∅ T A ↓! O ↓! T A ↓! ↑ ↓! ∅ T A ↓! O ↓! T T ∅ ↓! ↑ ↓! A T ↓! O ↓! A T ∅ ↓! ↑ ↓! A T ↓! O ↓! A T ∅ ↓! ↑ ↓! A T ↓! O ↓! A C O ↑ ↓! ↓! G C ↓! ↑ ↓! G C O ↑ ↓! ↓! G 5 3 C ↓! ↑ ↓! G 5 3 C O ↑ ↓! ↓! G 5 3 C ↓! ↑ ↓! G 3 5 3