This course provides an in-depth study of protein structure and function, focusing on the primary, secondary, tertiary, and quaternary levels, as well as protein-ligand interactions, allostery, and enzyme catalysis. Key topics include:

Primary Structure:

• Amino Acid Composition: Understanding the building blocks of proteins and their significance.
• Sequence Determination: Methods for determining the amino acid sequence of proteins.
• Synthesis of Peptides: Techniques for synthesizing peptides and the importance of primary structure.
• Covalent Modification: Various covalent modifications of polypeptides and their functional implications.

Secondary Structure:

• Peptide Bond: Structural implications of the peptide bond.
• Random Polymers: Characteristics of random polypeptide chains.
• Ramachandran Plot: Understanding permissible angles in polypeptide chains.
• Regular Conformations: Detailed study of α-helix, β-pleated sheets, and other helices (e.g., 3₁₀-helix).
• Super-Secondary Structures: Structures such as the coiled-coil α-helix.
• Fibrous Proteins Examples: Examination of α-keratins, silk fibroin, and collagen.

Tertiary Structure:

• Protein Folding: Evidence for and mechanisms of protein folding and unfolding.
• Structural Determination: Techniques such as X-ray crystallography to determine protein structures.
• Reverse Turns: Understanding β-turns and their role in protein folding.
• Super-Secondary Structures: Study of motifs, domains, and the differentiation between protein interiors and exteriors.
• Example: Detailed analysis of myoglobin.

Quaternary Structure:

• Aggregation: Mechanisms of protein aggregation into quaternary structures.
• Example: Detailed study of haemoglobin.

Protein-Ligand Interactions:

• Binding Sites: Examination of binding sites in haemoglobin and myoglobin.
• Oxygen and Carbon Monoxide Binding: Mechanisms of oxygen and carbon monoxide binding, and the micro-environment of haem iron.
• Hill Plot: Analysis of cooperative binding.
• Protein Engineering: Techniques and applications in modifying protein functions.

Allostery:

• Binding Site Interactions: Interaction between binding sites.
• Theoretical Models:
  • MWC Model: Mond-Wyman-Changeux concerted mechanism.
  • KNF Model: Koshland-Nemethy-Filmer sequential model.
• Allosteric Properties of Haemoglobin: Mechanisms of cooperative binding of oxygen, the Bohr effect, and binding of 2,3-bisphosphoglycerate (BPG).

Mechanism of Enzyme Catalysis:

• Catalysis Types: General acid-base catalysis and covalent catalysis.
• Coenzyme Catalysis: Role of coenzymes such as pyridoxal phosphate, thiamine pyrophosphate, ATP, coenzyme A, NAD(P)+, FAD/FMN.
• Enzyme Structure and Mechanism: Detailed study of selected enzymes.
  • Examples: Dehydrogenases, proteases, ribonuclease, lysozyme, glycolytic enzymes like phosphofructokinase (PFK).

Physical Forces:

• Maintaining Structure: Analysis of the physical forces (e.g., hydrogen bonds, hydrophobic interactions, van der Waals forces, ionic interactions) responsible for maintaining protein structures.