This review examines protein complexes in the Brookhaven Protein Databank to understand the principles governing protein-protein interactions. The study focuses on four types of complexes: homodimeric proteins, heterodimeric proteins, enzyme-inhibitor complexes, and antibody-protein complexes. The analysis highlights differences in their biological roles and structural characteristics. 1. **Introduction**: - Protein complexes are essential for many biological functions. - Complexes are categorized into homocomplexes (permanent and optimized) and heterocomplexes (nonobligatory and environment-dependent). - The distribution of multimeric states in the PDB is biased towards small monomers, with trimers being less common than tetramers. 2. **Characterization of Protein-Protein Interfaces**: - **Size and Shape**: Interface size is measured by ΔASA, with larger interfaces generally corresponding to larger subunits. - **Planarity**: Heterocomplexes have more planar interfaces compared to homodimers. - **Complementarity**: The gap index measures the complementarity between interacting surfaces, with homodimers and enzyme-inhibitor complexes showing higher complementarity. - **Residue Interface Propensities**: Hydrophobic residues are more prevalent in homodimer interfaces, while polar residues are more common in heterocomplexes. - **Hydrophobicity Including Hydrogen Bonding**: Heterocomplex interfaces are less hydrophobic due to the need for independent monomeric existence. - **Segmentation and Secondary Structure**: Interfaces vary in segment number and secondary structure composition, with β sheets often involved in specific interactions. 3. **Patch Analysis of Protein Surfaces in Homodimers**: - A patch analysis method is used to identify potential interface regions on protein surfaces. - The accessible surface area is the most discriminatory parameter for identifying interface regions. - The method can correctly identify over 70% of interface regions in homodimers. 4. **Discussion**: - The review emphasizes the importance of considering the type of protein-protein complex when characterizing interfaces. - The study highlights the need for further research to extend the analysis to higher-order complexes and to include factors like conformational changes and binding constants. - The implications of a better understanding of protein-protein interactions for therapeutic and environmental applications are significant. The review provides a comprehensive analysis of protein-protein interactions, emphasizing the importance of understanding the biological roles and structural characteristics of different types of complexes.This review examines protein complexes in the Brookhaven Protein Databank to understand the principles governing protein-protein interactions. The study focuses on four types of complexes: homodimeric proteins, heterodimeric proteins, enzyme-inhibitor complexes, and antibody-protein complexes. The analysis highlights differences in their biological roles and structural characteristics. 1. **Introduction**: - Protein complexes are essential for many biological functions. - Complexes are categorized into homocomplexes (permanent and optimized) and heterocomplexes (nonobligatory and environment-dependent). - The distribution of multimeric states in the PDB is biased towards small monomers, with trimers being less common than tetramers. 2. **Characterization of Protein-Protein Interfaces**: - **Size and Shape**: Interface size is measured by ΔASA, with larger interfaces generally corresponding to larger subunits. - **Planarity**: Heterocomplexes have more planar interfaces compared to homodimers. - **Complementarity**: The gap index measures the complementarity between interacting surfaces, with homodimers and enzyme-inhibitor complexes showing higher complementarity. - **Residue Interface Propensities**: Hydrophobic residues are more prevalent in homodimer interfaces, while polar residues are more common in heterocomplexes. - **Hydrophobicity Including Hydrogen Bonding**: Heterocomplex interfaces are less hydrophobic due to the need for independent monomeric existence. - **Segmentation and Secondary Structure**: Interfaces vary in segment number and secondary structure composition, with β sheets often involved in specific interactions. 3. **Patch Analysis of Protein Surfaces in Homodimers**: - A patch analysis method is used to identify potential interface regions on protein surfaces. - The accessible surface area is the most discriminatory parameter for identifying interface regions. - The method can correctly identify over 70% of interface regions in homodimers. 4. **Discussion**: - The review emphasizes the importance of considering the type of protein-protein complex when characterizing interfaces. - The study highlights the need for further research to extend the analysis to higher-order complexes and to include factors like conformational changes and binding constants. - The implications of a better understanding of protein-protein interactions for therapeutic and environmental applications are significant. The review provides a comprehensive analysis of protein-protein interactions, emphasizing the importance of understanding the biological roles and structural characteristics of different types of complexes.