Structural Biology – Easy Notes

Definition

Structural biology is the study of the 3D structures of macromolecules (like proteins and nucleic acids) at the atomic level.
👉 It explains structure, function, dynamics, and interactions of biomolecules.

7.1 Applications of Structural Biology

Structural biology is very useful in medical research and drug development.

1. Determining Active Sites and Domains

Active site = specific region of an enzyme where the substrate binds.
Domain = distinct structural unit in a protein that has its own function.

🔹 Examples:

HIV-1 reverse transcriptase → has two domains:

Polymerase domain (makes DNA).
RNase H domain (breaks RNA).

Serine protease → structure shows a clear active site that cuts peptide bonds.

👉 Knowing these sites helps in designing antiviral and enzyme-targeting drugs.

2. Identifying Drug Targets

Structural biology finds exact binding spots for drugs on disease-causing molecules.
These spots are usually proteins.

🔹 Example:

COVID-19 spike protein (SARS-CoV-2) → studied as a drug target.
Knowing its 3D shape helped scientists design vaccines & medicines that block the spike protein → prevents virus entry.

3. Understanding Host–Pathogen Interactions

Structural biology shows how pathogens (viruses/bacteria) attach to host cells.
🔹 Example:
Coronavirus spike protein attaches to a receptor on human cells.
Scientists studied both → discovered the exact binding mechanism.
Drugs/vaccines were made to block this interaction → stopping virus entry.

4. Identifying Protein Misfolding

Proteins work only if folded correctly into 3D shapes.
Misfolding → loss of function → diseases.
🔹 Examples of diseases caused by protein misfolding:
Cystic fibrosis
Parkinson’s disease
Alzheimer’s disease

👉 Structural biology explains folding pathways and helps in designing treatments.

Brief Explanation of Diseases

Cystic Fibrosis (CF)

A genetic disorder.
Caused by mutation in the CFTR protein → misfolding leads to thick, sticky mucus.
Affects lungs, pancreas, and digestive system.
Leads to breathing problems and infections.

Parkinson’s Disease

A neurodegenerative disorder.
Caused by misfolding of alpha-synuclein protein → forms harmful clumps in brain.
Damages nerve cells that make dopamine.
Symptoms: shaking, stiffness, slow movements.