This set of Bioinformatics Multiple Choice Questions & Answers (MCQs) focuses on “Protein Structure Classification”.
1. The classification results from both systems, SCOP and CATH are quite dissimilar.
Explanation: Due to the differences in classification criteria, one might expect that there would be huge differences in classification results. In fact, the classification results from both systems are quite similar. Exhaustive analysis has shown that the results from the two systems converge at about 80% of the time. In other words, only about 20% of the structure fold assignments are different.
2. The first step in structure classification is to remove redundancy from databases.
Explanation: Among the tens of thousands of entries in PDB, the majority of the structures are redundant as they correspond to structures solved at different resolutions, or associated with different ligands or with single-residue mutations. The redundancy can be removed by selecting representatives through a sequence alignment–based approach.
3. The second step in structure classification is to separate structurally distinct domains within a structure.
Explanation: Because some proteins are composed of multiple domains, they must be subdivided before a sensible structural comparison can be carried out. This domain identification and separation can be done either manually or based on special algorithms for domain recognition.
4. The last step in structure classification involves grouping proteins/domains of similar structures.
Explanation: Once multidomain proteins are split into separate domains, structure comparison can be conducted at the domain level, either through manual inspection, or automated structural alignment, or a combination of both. This step involves grouping proteins/domains of similar structures and clustering them based on different levels of resemblance in secondary structure composition and arrangement of the secondary structures in space.
5. Which of the following is untrue about SCOP?
a) It is a database for comparing and classifying protein structures
b) It is constructed almost entirely based on manual examination of protein structures
c) The proteins are grouped into hierarchies of classes, folds, superfamilies, and families
d) The SCOP families consist of proteins having low sequence identity (>30%)
Explanation: The SCOP families consist of proteins having high sequence identity (>30%). Thus, the proteins within a family clearly share close evolutionary relationships and normally have the same functionality. The protein structures at this level are also extremely similar.
6. Members within the ____ fold ______ have evolutionary relationships.
a) same, always
b) same, do not always
c) one, always
d) different, do not
Explanation: Folds consist of superfamilies with a common core structure, which is determined manually. This level describes similar overall secondary structures with similar orientation and connectivity between them. Members within the same fold do not always have evolutionary relationships. Some of the shared core structure may be a result of analogy. Classes consist of folds with similar core structures.
7. In CATH, Structural domain separation is carried by ___________
a) manual comparison only
b) computer programs only
c) human expertise only
d) a combined effort of a human expert and computer programs
Explanation: CATH classifies proteins based on the automatic structural alignment program SSAP as well as manual comparison. Structural domain separation is carried out also as a combined effort of a human expert and computer programs. Individual domain structures are classified at five major levels: class, architecture, fold/topology, homologous superfamily, and homologous family.
8. Which of the following is untrue about SCOP and CATH?
a) The definition for class in CATH is quite dissimilar to that in SCOP
b) The definition for class in CATH is based on secondary structure content
c) Architecture is a unique level in CATH, intermediate between fold and class
d) The definition for class in CATH is similar to that in SCOP
Explanation: The topology level is equivalent to the fold level in SCOP, which describes overall orientation of secondary structures and takes into account the sequence connectivity between the secondary structure elements. The homologous superfamily and homologous family levels are equivalent to the superfamily and family levels in SCOP with similar evolutionary definitions, respectively.
9. SCOP is _______ based on manual comparison of structures by human experts with no quantitative criteria to group proteins.
b) almost entirely
Explanation: It is argued that this approach offers some flexibility in recognizing distant structural relatives, because human brains may be more adept at recognizing slightly dissimilar structures that essentially have the same architecture. However, this reliance on human expertise also renders the method subjective. The exact boundaries between levels and groups are sometimes arbitrary.
10. CATH is a combination of manual curation and automated procedure, which makes the process less subjective.
Explanation: For example, in defining domains, CATH first relies on the consensus of three different algorithms to recognize domains. When the computer programs disagree, human intervention will take place. In addition, the extra Architecture level in CATH makes the structure classification more continuous. The drawback of the systems is that the fixed thresholds in structural comparison may make assignment less accurate.
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