This lecture covers the energetic determinants of protein folding, protein-protein interactions, and the concept of free energy. It discusses the importance of enthalpy, entropy, and heat capacity in protein folding, as well as equilibrium constants and examples like ATP hydrolysis and acid-base equilibrium. The lecture also explores the thermodynamic properties of proteins, focusing on unfolding reactions, melting temperature, and the measurement of enthalpy and entropy. Through examples and concepts like the hydrophobic effect, students learn how to compute pkas for residues within the protein environment.