Lecture 11

Question 1

How is the Position SOecific Scoring Matrix (PSSM) generated?

Answer 1

MSA of hits from the first iteration of PSI-BLAST; PSSM used in the second iteration

Question 1

Give 3 ways MSAs can give information on protein structure and function?

Answer 1

• Identify novel conserved domains
• Explore novel motifs and domains
• If crystal strucure is known, model others that are homologous (Homology Modelling)

Question 1

Why is MSA more computationally intensive than pairwise sequence alignment?

Answer 1

Scaling

Question 2

What is the central problem of protein structure?

Answer 2

Sequence doesn’t predict structuer

Question 3

In what way is progressive alignment a compromise?

Answer 3

Compromise between speed and accuracy

Question 4

Why is progressive alignment the prevailing strategy?

Answer 4

It’s fast and effective

Question 5

What is the 2-part strategy used in progressive alignments?

Answer 5

• Exhaustive pairwise alignments find closely related sequences
• Related sequences are progressively aligned by clustering

Question 6

Give 3 features of the Hidden Markov Model

Answer 6

• Model is hidden; only output is visible
• Doesn’t require pre-existing alignment; generates amino acid probabilities and aligns sequences
• Probabilities adjusted, when the model is run, to generate most likely path

Question 8

List 3 reasons for performing multiple sequence alignment (MSA)?

Answer 8

• Finding other related sequences
• Genome sequencing (assembly)
• Phylogenetic analysis

Question 9

How can Multiple Alignments (MAs) be used in phylogeny?

Answer 9

MAs of highly conserved sequences can be used to determine evolutionary relationships

Question 10

If given a Hidden Markov Model (HMM) of a sequence famiy and a query sequence, what can you calculate?

Answer 10

The probability that the HMM could emit the query; if this probability is high then query is likely a member of family

Question 12

What does Multiple Sequence Alignment (MSA) of homologius/orthologous genes reveal?

Answer 12

• Conserved nad variable regions
• Domain structure of proteins
• Likelystructure of novel protiens (Homology modelling)

Question 13

What 4 stages are involved in protein homology modelling?

Answer 13

• Align query protein with most similar sequence that has an X-ray crystal structure
• Superimpose, in 3 dimensions, the 2 structures; query and known
• Test the model (positions of backbone carbons, side chains)
• Propose model of query protein structure

Question 14

What might conserved protein domains correspond to?

Answer 14

Protein secondary structures