Protein Scoring Schemes Quiz

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Questions and Answers

What is the primary purpose of PAM matrices in protein sequence analysis?

To provide a framework for manual sequence alignment.

To assess the likelihood of amino acid substitutions over evolutionary time. (correct)

To identify phylogenetic trees without regard to sequence similarity.

To predict the three-dimensional structure of proteins.

How are substitution matrices like PAM250 generated?

By observing substitutions only in conserved regions.

Using sequences of proteins with less than 50% identity.

Through the manual alignment of sequences and analysis of amino acid substitution frequencies. (correct)

By analyzing random substitutions between unrelated proteins.

What does the number in PAM matrices (such as PAM100) indicate?

The total number of amino acids in a given protein structure.

The number of substitutions observed in a family of proteins.

The evolutionary distance between protein sequences. (correct)

The range of sequence identities across all family members.

What scoring range indicates that a substitution is less likely than random?

Negative scores Signup and view all the answers

What major limitation do PAM matrices have regarding evolutionary rates?

They do not consider differences between conserved and non-conserved regions. Signup and view all the answers

Which substitution matrix is typically preferred for local similarity searches?

BLOSUM62 Signup and view all the answers

What is the correct approach when comparing closely related proteins?

Use lower PAM or higher BLOSUM matrices Signup and view all the answers

What technique is recommended for aligning sequences without gaps?

Slide Window method Signup and view all the answers

What is an excluded option regarding disulfide bridges in amino acids?

Disulfide bridges can be replaced by any other residue. Signup and view all the answers

When is it appropriate to use matrices derived from observed substitutions?

For database searching Signup and view all the answers

What limitation does the Slide Window method face when dealing with gaps?

It cannot handle insertions and deletions effectively. Signup and view all the answers

Which BLOSUM matrix is commonly used as the default for searching databases?

BLOSUM62 Signup and view all the answers

What is the primary characteristic of matrices derived from structure alignment?

They allow comparison of distant proteins. Signup and view all the answers

What score is assigned for a match when scoring insertions and deletions?

1 Signup and view all the answers

Which of the following is NOT a technique used for alignment?

Random Sampling Signup and view all the answers

What is the disadvantage of manual alignment?

It is subjective. Signup and view all the answers

What is the purpose of the dot-matrix method?

To visually represent sequence alignment. Signup and view all the answers

In a dot-matrix alignment, which step does a diagonal move through a dot represent?

A match Signup and view all the answers

What value is assigned as the gap opening penalty in the scoring system?

3 Signup and view all the answers

Why might protein alignment be guided by secondary and tertiary structures?

To enhance accuracy. Signup and view all the answers

Which of the following best describes the function of the scoring system for insertions and deletions?

It rewards matches with high scores and penalizes mismatches. Signup and view all the answers

What does an E-value between 0.01 and 10 indicate about the match?

The match is insignificant but may suggest a tentative homology relationship. Signup and view all the answers

Which of the following statements about bit scores is true?

Bit scores are normalized values derived from raw alignment scores. Signup and view all the answers

In the bit score calculation formula S’ = (λ × S − lnK)/ ln2, what does 'S' represent?

The raw alignment score. Signup and view all the answers

What is the consequence of an E-value greater than 10?

The sequences are definitely unrelated or have extreme distant relationships. Signup and view all the answers

Which of the following is NOT a variant of the BLAST program?

megaBLAST Signup and view all the answers

How does BLAST differ from FASTA in terms of sensitivity?

FASTA provides higher specificity due to smaller window size scanning. Signup and view all the answers

Which aspect of the BLAST program is related to speed?

BLAST's use of a substitution matrix allows for faster processing. Signup and view all the answers

What role does the constant 'K' play in the bit score formula?

It is associated with the scoring matrix used. Signup and view all the answers

What type of phylogenetic tree reflects the amount of evolutionary change through proportional branch lengths?

Phylogram Signup and view all the answers

Which method is primarily concerned with maximizing the probability of observed data under a model of evolution?

Maximum Likelihood Signup and view all the answers

What is the primary purpose of a cladogram?

To represent the order of branching based on shared common ancestry Signup and view all the answers

Which type of tree illustrates the timing of evolutionary events with all tips equidistant from the root?

Ultrametric Tree Signup and view all the answers

What characteristic distinguishes a split network from a simple phylogenetic tree?

It can represent hybridization or gene flow Signup and view all the answers

Which method estimates the posterior distribution of trees based on prior knowledge?

Bayesian Inference Signup and view all the answers

What type of phylogenetic tree is a general term for tree-like diagrams that illustrate clustering or hierarchical relationships?

Dendrogram Signup and view all the answers

Which tree type does not have scaled branch lengths to evolutionary time?

Cladogram Signup and view all the answers

Study Notes

Scoring Schemes or Weight Matrices

PAM matrices (Percent Accepted Mutations) are derived from global alignments of protein families sharing at least 85% identity.
PAM matrices are used to calculate the evolutionary distance between protein families.
Construction of PAM matrices involves building a phylogenetic tree and ancestral sequences for each protein family.
PAM matrices are based on observed substitutions, but the problem of "chicken and egg" arises.
PAM matrices have limitations in considering different evolutionary rates between conserved and non-conserved regions.
BLOSUM matrices (Blocks Substitution Matrix) are more commonly used for local similarity searches and have better performance than PAM matrices.
BLOSUM matrices are based on aligned blocks of sequences that are more conserved than those used for PAM matrices.
Higher BLOSUM or lower PAM matrices are better for comparing closely related proteins.
Lower BLOSUM or higher PAM matrices are better for comparing distantly related proteins.
BLOSUM62 is the commonly used matrix for database searching.

Sequence Alignment Techniques

Manual alignment is a powerful tool for comparing similar sequences, but it is subjective and unscalable.
Dot-matrix methods are used to identify regions of similarity between two sequences.
Dot-matrix methods can be used to unravel information on the evolution of sequences.
Dynamic programming algorithms, such as the Smith-Waterman algorithm, are used to find the optimal alignment between two sequences.

Gaps in Pair-wise Alignment

Gaps are introduced in sequences to account for insertions and deletions.
Insertion and deletion are common in evolution, and ignoring them can lead to incorrect alignment.
Gap penalties are used to discourage the introduction of gaps in alignments.
Gap opening penalties are higher than gap extension penalties.

BLAST

BLAST (Basic Local Alignment Search Tool) is a powerful tool for searching databases for sequences that are similar to a query sequence.
BLAST uses a substitution matrix and a hashing procedure to find matching words or sequences.
BLAST is faster than FASTA and uses a low-complexity masking procedure to reduce false positives.
BLAST is sensitive enough to find weak homologies, but lower sensitivity may improve speed.

Phylogenetic Tree Types

Phylogenetic trees are used to represent the evolutionary relationship among species or organisms.
A cladogram shows the order of branching without considering the evolutionary time.
A phylogram shows the amount of evolutionary divergence based on branch lengths.
An ultrametric tree or chronogram shows the timing of evolution where all tips are equidistant from the root.
A dendrogram is a general term for tree-like diagrams used to illustrate clustering or hierarchical relationships.

Character-Based Methods

Maximum parsimony (MP) methods select the tree that requires the least number of evolutionary changes.
Maximum likelihood (ML) methods find the tree that maximizes the probability of the observed data given a model of evolution.
Bayesian inference is a probabilistic approach that uses the likelihood of observed data and prior knowledge to estimate the posterior distribution of trees.

Clustering-Based Methods

Hierarchical clustering groups sequences into clusters and produces dendrograms that resemble phylogenetic trees, but may not reflect true evolutionary relationships.

Network-Based Methods

Split networks can handle complex relationships, such as hybridization or gene flow, that are not easily represented by a simple tree.

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Description

Test your knowledge on PAM and BLOSUM matrices used in protein alignment and evolutionary studies. Explore how these matrices differ in their construction and application in calculating evolutionary distances. Understand the strengths and limitations of each scoring scheme with this informative quiz.