Chapter 12: Structural and Computational Biology

Select the correct answer:

1. The function of protein is very much dependent on its:

A. size

B. number of amino acids

C. 3D structure

D. types of amino acids

Answer: C. 3D structure

Explanation: The function of a protein is determined by its three-dimensional (3D) shape. The specific folding of the polypeptide chain creates the active sites and binding surfaces necessary for its biological role.

2. Structure of biomolecules can be very helpful to understand the:

A. spread of diseases

B. mechanism of diseases

C. cause of diseases

D. symptoms of diseases

Answer: B. mechanism of diseases

Explanation: Understanding the structure of biomolecules (proteins, nucleic acids) helps in elucidating the molecular mechanisms underlying diseases, such as how a mutated protein malfunctions.

3. Lock and key model is applicable to:

A. active site of enzyme and substrate

B. hormones and their receptors

C. antigens recognized by antibodies

D. all of above

Answer: D. all of above

Explanation: The lock and key model describes specific molecular recognition, which applies to enzyme-substrate binding, hormone-receptor binding, and antigen-antibody binding.

4. Targeted therapies can be more effective against:

A. bacterial infections

B. viral infections

C. metabolic diseases

D. syndromes

Answer: C. metabolic diseases

Explanation: Targeted therapies are designed to interfere with specific molecules involved in disease processes. They are particularly effective against diseases with a defined molecular target, such as certain metabolic diseases and cancers. (Note: They are also used for some bacterial and viral infections, but the question likely refers to the specificity of molecular targets).

5. There are more than 200 types of cancers. Proper treatment of a specific cancer requires personalized medicines because each cancer has a:

A. different name

B. different effect on each person

C. specific cell surface marker

D. different set of symptoms

Answer: C. specific cell surface marker

Explanation: Personalized medicine for cancer relies on identifying specific molecular markers (e.g., cell surface receptors) unique to the cancer cells, allowing for targeted therapy.

6. X-ray crystallography cannot be done on liquid or gaseous sample because:

A. 3D electron maps are formed on solids

B. X-ray diffraction is done on crystals

C. solutions on evaporation form solids

D. gases on slow cooling can form liquids

Answer: B. X-ray diffraction is done on crystals

Explanation: X-ray crystallography requires a crystalline sample to produce a diffraction pattern. The regular, repeating arrangement of atoms in a crystal is necessary to amplify the scattered X-rays into a detectable pattern.

7. As a Pakistani student you can access the Protein Data Bank:

A. by using VPN

B. after paying require fee

C. freely via Internet

D. if you get reference letter from concerned department

Answer: C. freely via Internet

Explanation: The Protein Data Bank (PDB) is a freely accessible online database of protein structures. It can be accessed by anyone with an internet connection.

8. The rRNA sequence of all organisms has homology, it shows that all organisms:

A. use ribosomes for protein

B. have same size of ribosomes

C. have evolved from common ancestor

D. have same types of ribosomes

Answer: C. have evolved from common ancestor

Explanation: Homology in rRNA sequences across diverse organisms indicates that these sequences have been conserved throughout evolution, suggesting a common evolutionary origin.

9. Structural homology of myoglobin in different mammals is helpful to these organisms as:

A. it gives their meat red colour

B. similar shapes are related with similar functions

C. myoglobin can replace haemoglobin function when required

D. different mammals eat each other so they can use it in their bodies

Answer: B. similar shapes are related with similar functions

Explanation: Structural homology (similar 3D structures) often implies similar functions. Myoglobin's conserved structure across mammals ensures efficient oxygen storage in muscles.

10. The Protein Data Bank provide information about:

A. all molecules

B. all proteins

C. all enzymes

D. all biomolecules

Answer: D. all biomolecules

Explanation: The Protein Data Bank (PDB) primarily archives structural data of proteins and nucleic acids (biomolecules), not all molecules.

1. How is the structure of molecule related with its function?

Answer: The structure of a molecule, especially its three-dimensional shape, is directly related to its function. For example, the

specific folding of a protein creates an active site that is complementary to its substrate, enabling catalysis. Similarly, the double helix structure of DNA allows it to store and replicate genetic information. The shape of a hormone determines which receptor it can bind to. Any change in structure (denaturation or mutation) can lead to loss of function.

2. How does structural biology give hope to cancer treatment research?

Answer: Structural biology provides hope for cancer treatment by revealing the precise 3D structures of proteins involved in cancer development and progression. This allows researchers to design drugs that specifically target these proteins, inhibiting their activity. For example, understanding the structure of kinases has led to targeted therapies like imatinib for leukemia. It also helps in understanding drug resistance mechanisms. This structure-based drug design is more precise and less toxic than traditional chemotherapy.

3. If you want to study the structure of pepsin enzyme, what will you do?

Answer: To study the structure of pepsin, I would use X-ray crystallography. First, I would purify the pepsin protein. Then, I would crystallize it under controlled conditions. The crystals would be exposed to X-rays, and the resulting diffraction pattern would be collected. Using computational methods, I would construct a 3D electron density map and build an atomic model of the enzyme. Alternatively, Cryo-Electron Microscopy (Cryo-EM) could be used if crystals are difficult to obtain.

4. What fields of science are related to computational biology?

Answer: Computational biology is an interdisciplinary field that combines biology, computer science, mathematics, and statistics. Related fields include:

Bioinformatics: Managing and analyzing biological data. Computational Genomics: Analyzing genomes. Structural Bioinformatics: Predicting and analyzing protein structures. Systems Biology: Modeling complex biological systems. Cheminformatics: Analyzing chemical data. Biostatistics: Applying statistics to biological data.

5. Define structural biology, crystallography, computational biology, PDB, sequence homology and structural homology.

Answer:

Structural Biology: The branch of biology focused on the molecular structure of biological macromolecules. Crystallography: The science of determining the arrangement of atoms in crystalline solids, used for protein structure determination. Computational Biology: The use of computational methods to analyze and model biological data. PDB: Protein Data Bank, a database of 3D structures of proteins and nucleic acids. Sequence Homology: Similarity in the amino acid or nucleotide sequences of different molecules, indicating common ancestry. Structural Homology: Similarity in the 3D structures of different molecules, often related to similar functions.

1. Why is it necessary to determine the structure of biomolecules?

Answer:

Determining the structure of biomolecules is essential for understanding their function, interactions, and roles in health and disease. The structure of a biomolecule dictates its function, and knowledge of the structure is crucial for many applications.

1. Understanding Function:

The 3D structure of a protein determines its active site, binding properties, and catalytic activity. For example, the structure of hemoglobin explains its oxygen-binding capacity.

2. Drug Design and Discovery:

Knowledge of the structure of a target protein (e.g., an enzyme or receptor) allows for the rational design of drugs that bind specifically to it. This is the basis of structure-based drug design, leading to more effective and less toxic drugs.

3. Understanding Diseases:

Many diseases are caused by mutations that alter protein structure and function. Determining the structure of mutant proteins helps in understanding the molecular basis of diseases like cancer, Alzheimer's, and cystic fibrosis.

4. Biotechnology and Engineering:

Structural knowledge is used to engineer proteins with novel functions, such as industrial enzymes or therapeutic antibodies.

5. Evolutionary Studies:

Comparing structures of biomolecules from different organisms reveals evolutionary relationships and conserved functional domains.

6. Vaccine Development:

Understanding the structure of viral surface proteins aids in designing vaccines that elicit protective immune responses.

In summary, determining the structure of biomolecules is fundamental to understanding life processes, developing therapeutics, and advancing biotechnology. It bridges the gap between sequence and function.

2. Describe the steps of X-ray crystallography.

Answer: X-ray crystallography is a powerful technique used to determine the atomic and molecular structure of a crystal. The steps are:

1. Protein Purification:

The protein of interest is isolated and purified to homogeneity.

2. Crystallization:

The purified protein is subjected to conditions that promote the formation of crystals. This is often the most challenging step. Methods include vapor diffusion (hanging drop, sitting drop), batch crystallization, and dialysis.

3. Data Collection:

The crystal is mounted and exposed to a beam of X-rays. The electrons in the crystal scatter the X-rays, producing a diffraction pattern. The diffraction pattern is recorded on a detector.

4. Data Processing:

The diffraction images are processed to determine the intensities and positions of the spots.

This involves indexing, integration, and scaling of the data.

5. Phase Problem:

The phase information is lost during data collection. This is the "phase problem." Methods to solve the phase problem include Multiple Isomorphous Replacement (MIR), Multi-wavelength Anomalous Dispersion (MAD), and Molecular Replacement (MR).

6. Electron Density Map:

Using the amplitudes and phases, an electron density map is calculated. This map shows the distribution of electrons in the unit cell.

7. Model Building and Refinement:

An atomic model of the protein is built into the electron density map using computer graphics. The model is refined iteratively to improve its agreement with the experimental data.

8. Validation:

The final model is validated using various criteria to ensure its accuracy.

In summary, X-ray crystallography involves purification, crystallization, data collection, phase determination, model building, and refinement to determine the 3D structure of a protein.

3. Differentiate between sequence and structural homology.

Answer: Sequence homology and structural homology are two related but distinct concepts in molecular biology.

Key Points:

Sequence homology can exist without structural homology (e.g., proteins with similar sequences but different folds). Structural homology can exist without detectable sequence homology (e.g., proteins with different sequences but similar folds). Structural homology is often used to infer function when sequence homology is low.

In summary, sequence homology compares linear sequences, while structural homology compares 3D folds. Both are used to study evolutionary relationships and protein function.