Assignment 1. Protein structure analysis.

1) Select four proteins with known structures which belong to the same family and have pairwise sequence identity of no more than 65%. The length of each protein should be less than 150 residues and structure resolution better than 1.6Å.

2) Build a multiple sequence alignment and all possible pairwise structure alignments for these proteins. Plot the values of structure similarity against sequence similarity for all pairs. Evaluate and discuss correlation between sequence and structure similarity.

3) Locate at least one fragment of high sequence similarity and one fragment of low sequence similarity in these proteins. Investigate correlations between structure and sequence similarity for these fragments. Describe a possible role of the secondary structure content in these correlations.

4) Identify functionally important site(s) in these proteins and their relationship to the structure conservation.

The report should be submitted by email as a Word or PDF file with the filename "b731_22_hw1_Your_Name.doc or .pdf". The string "b731_22_hw1_Your_Name" should be also included in the message subject line.

Due October 27, 2022.

Assignment 2. Protein modeling.

a) Select a sequence of a human enzyme from one of the protein sequence databases that has a homolog in PDB with at least 30%, but not more than 60% of sequence identity. (Recommended length of the selected sequence is 150-250 residues).

b) Predict the three-dimensional structure for the selected sequence using at least two methods, e.g., fold recognition and homology modeling (Phyre2, I-TASSER, RaptorX, SwissModel, Modweb, etc.).

c) Analyze the quality of your model using one of the structure validation or verification tools.

d) Evaluate separately one of the biologically important parts of the structure (e.g., an active site or binding site).

e) Introduce residue substitution(s) at one or more positions of your original sequence, which would likely affect the structure and/or function of this protein. Model the structure of this mutant and compare it with the structure of the wild type model.

f) Present the results of the modeling with description of all the steps and structure annotation in HTML format with interactive molecular visualization tools and post the files on your binf webspace.

Submit the URL by email with the string "b731_22_hw2" in the message subject line.

Due December 1, 2022.