@inbook {163322, title = {Cryo-Electron Microscopy in the Study of Protein{\textendash}Protein Interactions}, booktitle = { Computational Approaches in Drug Design }, volume = {42}, year = {2026}, pages = {43-76}, publisher = {Springer, Cham}, organization = {Springer, Cham}, chapter = {Cryo-Electron Microscopy in the Study of Protein{\textendash}Protein Interactions}, abstract = {

Protein{\textendash}protein interactions (PPIs) are fundamental to many biological processes, including signal transduction, gene regulation, maintenance of cellular homeostasis, and immune response. Understanding the molecular details of PPIs is vital for elucidating the mechanisms underlying cellular functions and diseases. Traditionally, techniques such as X-ray crystallography and nuclear magnetic resonance (NMR) have provided valuable structural information about PPIs. However, the investigation of protein complexes that are large, dynamic, flexible, or those associated with membranes has proven difficult to characterize structurally. Cryo-Electron Microscopy (Cryo-EM) and Cryo-Electron Tomography (Cryo-ET) have revolutionized the ability to visualize protein{\textendash}protein interactions increasingly at higher resolution and within cellular context. Despite its strengths, imaging with Electron Microscopy (EM) poses challenges in achieving high-resolution structures for small or heterogeneous complexes and requires substantial computational resources for data processing. Nonetheless, its ability to reveal atomic-level details of protein interactions makes it a crucial tool in structural biology and drug discovery. This chapter reviews recent advances in cryo-EM techniques, particularly in the study of PPIs.

}, keywords = {Cryo-EM, Cryo-ET, Drug discovery., Protein{\textendash}protein interaction, Structural biology}, isbn = {Print ISBN 978-3-032-07879-7}, issn = {Online ISBN 978-3-032-07880-3}, doi = {https://doi.org/10.1007/978-3-032-07880-3_3}, url = {https://link.springer.com/chapter/10.1007/978-3-032-07880-3_3}, author = {Trung Thach and Kutti R. Vinothkumar and Ramaswamy Subramanian} }