This set of Bioinformatics Multiple Choice Questions & Answers (MCQs) focuses on “Threading and Fold Recognition”.
1. There are a large number of protein folds available, compared to millions of protein sequences.
Explanation: There are only small number of protein folds available (<1,000), compared to millions of protein sequences. This means that protein structures tend to be more conserved than protein sequences. Consequently, many proteins can share a similar fold even in the absence of sequence similarities. This allowed the development of computational methods to predict protein structures beyond sequence similarities.
2. Threading or structural fold recognition predicts the structural fold of an unknown protein sequence by fitting the sequence into a structural database and selecting the best-fitting fold.
Explanation: To determine whether a protein sequence adopts a known three-dimensional structure fold relies on threading and fold recognition methods. The comparison emphasizes matching of secondary structures, which are most evolutionarily conserved. Therefore, this approach can identify structurally similar proteins even without detectable sequence similarity.
3. The algorithms used here can be classified into two categories, pairwise energy based and profile based.
Explanation: The pairwise energy–based method was originally referred to as threading and the profile-based method was originally defined as fold recognition. However, the two terms are now often used interchangeably without distinction in the literature.
4. In the pairwise energy based method, a protein sequence is searched for in a structural fold database to find the best matching structural fold using ______ criteria.
Explanation: The detailed procedure involves aligning the query sequence with each structural fold in a fold library. The alignment is performed essentially at the sequence profile level using dynamic programming or heuristic approaches. Local alignment is often adjusted to get lower energy and thus better fitting. The adjustment can be achieved using algorithms such as double-dynamic programming.
5. The next step in the pairwise energy based method is to build a crude model for the target sequence by replacing aligned residues in the template structure with the corresponding residues in the query.
Explanation: After the mentioned step, the last step is to calculate the energy terms of the raw model, which include pairwise residue interaction energy, solvation energy, and hydrophobic energy. Finally, the models are ranked based on the energy terms to find the lowest energy fold that corresponds to the structurally most compatible fold.
6. Which of the following is untrue about profile method?
a) A profile is constructed for a group of related protein structures
b) The propensity of amino acids in not in picture of this method
c) Statistical information from these aligned residues is then used to construct a profile
d) The structural profile is generated by the superimposition of the structures to expose corresponding residues
Explanation: The profile contains scores that describe the propensity of each of the twenty amino acid residues to be at each profile position. The profile scores contain information for secondary structural types, the degree of solvent exposure, polarity, and hydrophobicity of the amino acids. To predict the structural fold of an unknown query sequence, the query sequence is first predicted for its secondary structure, solvent accessibility, and polarity.
7. Because threading and fold recognition detect structural homologs ________ relying on sequence similarities, they have been shown to be _______ than PSI-BLAST in finding distant evolutionary relationships
a) without completely, far more sensitive
b) completely, far more sensitive
c) completely, less sensitive
d) without completely, less sensitive
Explanation: In many cases, they can identify more than twice as many distant homologs than PSI-BLAST. However, this high sensitivity can also be their weakness because high sensitivity is often associated with low specificity. The predictions resulting from threading and fold recognition often come with very high rates of false positives. Therefore, much caution is required in accepting the prediction results.
8. Which of the following is untrue about threading and fold recognition?
a) It assess the compatibility of an amino acid sequence with a known structure in a fold library
b) If the protein fold to be predicted does not exist in the fold library, the method won’t necessarily fail
c) If the protein fold to be predicted does not exist in the fold library, the method will fail
d) Threading and fold recognition do not generate fully refined atomic models for the query sequences
Explanation: A disadvantage compared to homology modeling lies in the fact that threading and fold recognition do not generate fully refined atomic models for the query sequences. This is because accurate alignment between distant homologs is difficult to achieve. Instead, threading and fold recognition procedures only provide a rough approximation of the overall topology of the native structure.
9. Which of the following is untrue about 3D-PSSM?
a) It is a web-based program that employs the structural profile method to identify protein folds
b) The profiles for each protein superfamily are constructed by combining multiple smaller profiles
c) A protein structural superfamily doesn’t have sequence-based PSI-BLAST profile
d) In initial steps, protein structures in a superfamily based on the SCOP classification are superimposed
Explanation: First, protein structures in a superfamily based on the SCOP classification are superimposed and are used to construct a structural profile by incorporating secondary structures and solvent accessibility information for corresponding residues. In addition, each member in a protein structural superfamily has its own sequence-based PSI-BLAST profile computed. These sequence profiles are used in combination with the structure profile to form a large superfamily profile in which each position contains both sequence and structural information.
10. Which of the following is true about Gen Threader?
a) It is a web-based program that uses a hybrid of the profile and pairwise energy methods
b) It is a web-based program that uses profile methods only
c) It is a web-based program that uses pairwise energy methods only
d) The initial step is quite dissimilar to 3D-PSSM
Explanation: The initial step is similar to 3D-PSSM; the query protein sequence is subject to three rounds of PSI-BLAST. The resulting multiple sequence hits are used to generate a profile. Its secondary structure is predicted using PSIPRED. Both are used as input for threading computation based on a pairwise energy potential method. The threading results are evaluated using neural networks that combine energy potentials, sequence alignment scores, and length information to create a single score representing the relationship between the query and template proteins.
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