2nd_Exam_Solutions_2007

2nd_Exam_Solutions_2007 - Second Exam Biochem 104b Question...

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Second Exam Biochem 104b Question 1 You work in a protein engineering lab and you want to redesign a protein to introduce a new hydrogen bond to a solvent exposed carbonyl oxygen. Using computer graphics you identify an alanine residue that, when replaced by a tyrosine, would allow the formation of that new hydrogen bond. However, there are two possible conformations for the new tyrosine side-chain. In conformation 1 the tyrosine can form the hydrogen bond to the desired solvent- exposed backbone carbonyl, but the aromatic ring remains solvent exposed on all sides. In conformation 2 the tyrosine side chain stacks on top of another aromatic side chain. It is not clear how closely the two side-chains will pack, but it is clear that in conformation 2 the interface between the two rings will be shielded completely from solvent. a) What interactions, if any, favor conformation 1 and 2. Answer: Conformation 1 would be favored by the hydrogen bond formed between the tyrosine residue and the carbonyl. However, formation of this hydrogen bond requires the disruption of other hydrogen bonds these two groups are forming with solvent. Therefore forming this hydrogen bond should have essentially no stabilizing effect. In conformation 2 we burry two hydrophobic surfaces. That of the tyrosine and that of the other aromatic side chain. The net effect is equivalent to burying an aromatic ring in a hydrophobic environment. b) Among those interactions there is one, for which the exact strength is hard to estimate. What is that interaction and why is it hard to estimate? Answer: If the packing of the two aromatic chains is very tight, we might also get substantial VDW interactions, but it would be hard to predict the magnitude of this interaction. The reason is the steep (1/r 6 ) distance dependence of the energy from VDW interactions, a small structural difference can make a large difference in the interaction energy. c)
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This note was uploaded on 09/21/2008 for the course BCHM 104 taught by Professor Miller during the Spring '07 term at Brandeis.

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2nd_Exam_Solutions_2007 - Second Exam Biochem 104b Question...

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