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Right answer is (c) ENERGY-based

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.

Correct choice is (c) There is no use of HEURISTIC alignment SEARCH programs

To explain I would say: The search can be performed using a heuristic pair wise alignment search program such as BLAST or FASTA. However, the use of DYNAMIC programming based search programs such as SEARCH or ScanPS can result in more sensitive search results. The relatively small size of the structural DATABASE means that the search time using the exhaustive method is still within reasonable limits, while giving a more sensitive result to ensure the best possible similarity hits.

Right answer is (a) True

To explain: In these loop modeling and side chain modeling steps, potential energy calculations are applied to improve the model. However, this does not guarantee that the entire raw homology model is free of structural irregularities such as unfavorable BOND ANGLES, bond lengths, or close ATOMIC contacts. There, this step is used. The goal of energy MINIMIZATION is to RELIEVE steric collisions and strains without significantly altering the overall structure.

Correct option is (c) A protein structural superfamily doesn’t have sequence-based PSI-BLAST PROFILE

The explanation is: 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.

Right choice is (b) In the sequence alignment for modeling, there are no regions PRODUCING gaps in sequence alignment

To explain I WOULD say: Closing the gaps requires loop modeling, which is a very difficult problem in homology modeling and is also a major source of error. Loop modeling can be CONSIDERED a mini–protein modeling problem by itself. Unfortunately, there are no mature methods AVAILABLE that can model loops reliably. Currently, there are two main techniques used to approach the problem: the database searching METHOD and the ab initio method.

Correct choice is (a) It is a web-based program that USES a hybrid of the PROFILE and pairwise energy methods

To elaborate: 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.

Right option is (a) True

To elaborate: HOWEVER, this approach is computationally prohibitive in most cases. In FACT, most current side chain prediction programs use the concept of rotamers, which are favored side chain torsion angles EXTRACTED from known PROTEIN crystal structures. In prediction of side chain conformation, only the possible rotamers with the LOWEST interaction energy with nearby atoms are selected.

The correct answer is (b) The propensity of amino acids in not in picture of this method

The best I can explain: 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.

Right answer is (a) PETRA is a web server that models loops using the database approach

To explain I would SAY: PETRA is a web server that uses the ab initio method to MODEL loops. For NINE to thirty residues, CODA uses FREAD prediction only.

Right choice is (d) Errors made in the alignment step can be corrected in the following modeling STEPS

BEST explanation: Incorrect alignment at this stage leads to incorrect designation of homologous residues and therefore to incorrect structural MODELS. Errors made in the alignment step cannot be corrected in the following modeling steps. Therefore, the best possible multiple alignment algorithms, such as Praline and T-Coffee should be USED for this PURPOSE.

The correct choice is (a) True

To explain I would say: Usually, many different alternative segments that fit the ENDPOINTS of the stems are AVAILABLE. The best loop can be selected based on sequence similarity as well as MINIMAL STERIC clashes with the NEIGHBORING parts of the structure. The conformation of the best matching fragments is then copied onto the anchoring points of the stems.

The CORRECT option is (d) It doesn’t involve the EVOLUTIONARY distances anywhere

The explanation: As the name suggests, HOMOLOGY modeling PREDICTS protein structures based on sequence homology with known structures. Homology modeling produces an all-atom model based on alignment with template proteins.

The correct option is (a) True

Best 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.

The CORRECT CHOICE is (a) True

To elaborate: Current ab INITIO algorithms are not yet able to accurately simulate the protein folding process. They work by using some type of heuristics. Because the native STATE of a protein structure is near energy minimum, the prediction programs are thus DESIGNED using the energy minimization principle.

The correct CHOICE is (c) The AB initio prediction method attempts to produce all-atom protein MODELS based on sequence information alone with some aid of known protein structures

Easy explanation: Alongside the advantages, because the physicochemical laws governing protein folding are not yet well understood, the energy functions used in the ab initio prediction are, at PRESENT, rather inaccurate. The folding problem remains one of the greatest challenges in bioinformatics today.

Correct option is (a) without COMPLETELY, far more sensitive

Easy 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.

Correct answer is (b) SECONDARY, three

To explain I would SAY: Through RANDOM combinations of the FRAGMENTS, a large number of models are built and their overall ENERGY potentials calculated. The conformation with the lowest global free energy is chosen as the best model.

The correct answer is (a) True

To EXPLAIN: These ALGORITHMS search for every possible conformation to find the ONE with the lowest GLOBAL energy. However, searching for a fold with the absolute minimum energy may not be valid in reality. This contributes to one of the fundamental flaws of this APPROACH. In addition, searching for all possible structural conformations is not yet computationally feasible.

Correct ANSWER is (b) If the protein FOLD to be predicted does not exist in the fold library, the METHOD won’t necessarily fail

To explain: 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.

Correct option is (a) True

The best 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.

The correct choice is (a) True

Explanation: This in fact relies on a “mini-threading” METHOD. The method first breaks down the query sequence into MANY very short SEGMENTS (THREE to nine residues) and predict the SECONDARY structure of the small segments using a Hidden Markov model–based program, HMMSTR.

Right option is (b) False

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.

The correct option is (a) True

To explain: Only limited ENERGY minimization is RECOMMENDED (a few hundred ITERATIONS) to remove major errors, such as short BOND distances and close atomic clashes. Key conserved residues and those involved in cofactor binding have to be RESTRAINED if necessary during the process.

Correct choice is (c) If the two residues differ, everything other than the backbone atoms can be copied

The best I can EXPLAIN: Option “Once OPTIMAL alignment is achieved, residues in the ALIGNED regions of the target protein can assume a similar structure as the template proteins” and “Coordinates of the corresponding residues of the template proteins can be simply copied onto the target protein” MEAN the same. If the two residues differ, only the backbone atoms can be copied. The side chain atoms are rebuilt in a subsequent procedure.

In backbone modeling, it is simplest to use only one template structure. The structure with the best quality and highest resolution is normally chosen if multiple OPTIONS are available.

The correct option is (a) True

Easy 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.