This set of Bioinformatics Multiple Choice Questions & Answers (MCQs) focuses on “Protein Structure Comparison”.
a) The comparative approach is important in finding remote protein homologs
b) Protein structures have a much higher degree of conservation than the sequences
c) Protein structures have a much lesser degree of conservation than the sequences
d) Proteins can share common structures even without sequence similarity
Explanation: structure comparison is one of the fundamental techniques in protein structure analysis. Structure comparison can often reveal distant evolutionary relationships between proteins, which is not feasible using the sequence-based alignment approach alone. In addition, protein structure comparison is a prerequisite for protein structural classification into different fold classes.
2. The intermolecular approach is normally applied to relatively _____ structures.
Explanation: The algorithmic approaches to comparing protein geometric properties can be divided into three categories: the first superposes protein structures by minimizing intermolecular distances; the second relies on measuring intramolecular distances of a structure; and the third includes algorithms that combine both intermolecular and intramolecular approaches.
3. Which of the following is incorrect about intermolecular approach?
a) This procedure starts with identifying equivalent residues or atoms
b) After residue–residue correspondence is established, one of the structures is moved laterally and vertically toward the other structure to allow the two structures to be in the same location
c) The structures are rotated relative to each other around the three-dimensional axes
d) The rotation doesn’t depend on the intermolecular distance
Explanation: The rotation continues until the shortest intermolecular distance is reached. At this point, an optimal superimposition of the two structures is reached. After superimposition, equivalent residue pairs can be identified, which helps to quantitate the fitting between the two structures.
Explanation: An important measurement of the structure fit during superposition is the distance between equivalent positions on the protein structures. This requires using a least square-fitting function called root mean square deviation (RMSD), which is the square root of the averaged sum of the squared differences of the atomic distances. Here D is the distance between coordinate data points and N is the total number of corresponding residue pairs.
Explanation: In practice, only the distances between Cα carbons of corresponding residues are measured. The goal of structural comparison is to achieve a minimum RMSD. However, the problem with RMSD is that it depends on the size of the proteins being compared. For the same degree of sequence identity, large proteins tend to have higher RMSD values than small proteins when an optimal alignment is reached. Recently, a logarithmic factor has been proposed to correct this size-dependency problem. This new measure is called RMSD100.
6. The intramolecular approach does not depend on sequence similarity between the proteins to be compared.
Explanation: The intramolecular approach relies on structural internal statistics and therefore does not depend on sequence similarity between the proteins to be compared. In addition, this method does not generate a physical superposition of structures, but instead provides a quantitative evaluation of the structural similarity between corresponding residue pairs.
7. Which of the following is incorrect about the intramolecular approach?
a) The method works by generating a distance matrix between residues of the same protein
b) It generates a string between residues of the same protein
c) In comparing two protein structures, the distance matrices from the two structures are moved relative to each other to achieve maximum overlaps
d) By overlaying two distance matrices, similar intramolecular distance patterns representing similar structure folding regions can be identified
Explanation: For the ease of comparison, each matrix is decomposed into smaller submatrices consisting of hexapeptide fragments. To maximize the similarity regions between two structures, a Monte Carlo procedure is used. By reducing three-dimensional information into two-dimensional information, this strategy identifies overall structural resemblances and common structure cores.
8. Which of the following is incorrect about Multiple Structure Alignment?
a) The alignment strategy is different than the Clustal sequence alignment using a progressive approach
b) All structures are first compared in a pairwise fashion
c) A distance matrix is developed based on structure similarity scores such as RMSD
d) The aligned structures create a median structure that allows other structures to be progressively added for comparison based on the hierarchy described in the guide tree
Explanation: In addition to pairwise alignment, a number of algorithms can also perform multiple structure alignment. The alignment strategy is similar to the Clustal sequence alignment using a progressive approach. When all the structures in the set are added, this eventually creates a multiple structure alignment.
a) It is a web server that uses an intramolecular distance–based method
b) Matrices are built based on the Cβ distances of all residue pairs
c) Dynamic programming approach is not used here
d) Dynamic programming approach is used
Explanation: When comparing two different matrices, a dynamic programming approach is used to find the path of residue positions with optimal scores. The dynamic programming is applied at two levels, one at a lower level in which all residue pairs between the proteins are compared and another at an upper level in which subsequently identified equivalent residue pairs are processed to refine the matching positions. An SSAP score is reported for structural similarity. A score above 70 indicates a good structural similarity.
10. VAST is a web server that performs alignment using intramolecular approaches only
Explanation: VAST (Vector Alignment Search Tool) is a web server that performs alignment using both the inter- and intramolecular approaches. The superposition is based on information of directionality of secondary structural elements (represented as vectors). Optimal alignment between two structures is defined by the highest degree of vector matches.
Sanfoundry Global Education & Learning Series – Bioinformatics.
To practice all areas of Bioinformatics, here is complete set of 1000+ Multiple Choice Questions and Answers.