The Three Functional States of Proteins

Dr. Timir Tripathi is a Professor of Molecular Biology, School of Life Sciences, North-Eastern Hill University, Shillong, India. He previously held positions as Regional Director of IGNOU in Kohima and a Senior Assistant Professor in the Department of Biochemistry at NEHU. His research focuses on protein–substrate interactions, conformational dynamics, and the regulatory roles of non-catalytic domains. He is especially interested in intrinsically disordered and phase-separated proteins, their roles in disease, and, more recently, molecular memory, adaptive learning, and intelligence in proteins. Professor Tripathi has received several awards and is an Associate Fellow of the Indian National Science Academy, New Delhi, and an elected member of the National Academy of Sciences, India. He is a section editor of Elsevier's International Journal of Biological Macromolecules and has published five books with Elsevier.Prof. Vladimir N. Uversky, PhD, DSc, FRSB, FRSC, F.A.I.M.B.E., Professor at the Department of Molecular Medicine, Morsani College of Medicine, University of South Florida (USF), is a pioneer in the field of protein intrinsic disorder. He has made a number of groundbreaking contributions in the field of protein folding, misfolding, and intrinsic disorder. He obtained his PhD from Moscow Institute of Physics and Technology and D.Sc. from the Institute of Experimental and Theoretical Biophysics, Russian Academy of Sciences. Since 2010, Professor Uversky has worked at University of South Florida, where he works on various aspects of protein intrinsic disorder phenomenon and analysis of protein folding and misfolding processes. He has authored over 1250 scientific publications and edited several books and book series on protein structure, function, folding, misfolding, and intrinsic disorder. He also servs as an editor in a number of scientific journals.

"This book’s purpose is to serve, first and foremost, as an entry point for students and scientists new to the field of protein thermodynamics and phase transitions. [It] uses a combination of 'foundational concepts and recent advancements in the field' to appeal to a wide audience from various academic disciplines.... [It] provides an effective survey of the protein structural biology and dynamics, starting with Emil Fischer’s seminal 'lock and key' model for enzyme-substrate interactions.... described with clear and flowing prose complemented by a modest number of illustrations and many biomedically-relevant examples.... What sets this title apart is its organizing leitmotif, that the incredible functional and structural versatility of proteins can be shoe-horned into a three state-model. For those who favor or are open to its central thesis, this book provides an informative and well-written guide." ©Doody's Review Service, 2025, Peter Kennelly, PhD (Virginia Tech)

• 1. The three functional states of proteins: Beyond the classical “lock-and-key” paradigm2. Ordered proteins and structure-function relationship: Classical view3. Binding of a substrate (“lock and key”) and conformational adaption (“induced fit”) are different stages of enzyme action4. Intrinsically disordered proteins: Functionality of chaos5. Protein Conformation-based Phenotypic Switching and Implications in the Origin and Evolution of Multicellularity6. Hybrid proteins: Fusion chimeras and natural wonders7. Functional protein oligomers8. Fuzzy complexes9. SMARTQ: Single Molecule Amyloid fibRil Tracking and Quantification. A method for accurately imaging, tracking and quantifying the growth of individual amyloid fibrils using TIRF10. Structural Polymorphism in Amyloids – States within Proteins’ Solid-State11. Liquid-Liquid Phase Separation, Biomolecular Condensates and Membraneless Organelles: A Novel Blueprint of Intracellular Organization12. Physical principles and molecular interactions underlying protein phase separation13. Various levels of phase transitions in the protein universe14. Targeting phase-separated protein states for drug discovery15. Protein hydrogels: Structure, Characteristics, and Applications16. Interactions among the three protein states17. Protein frustration and fuzziness in the three functional states18. Thermoresponsive intrinsically disordered protein polymers19. The evolution and exploration of intrinsically disordered and phase-separated protein states20. Computational modelling of intrinsically disordered and phase separated protein states21. Molecular dynamics simulations of intrinsically disordered, fuzzy complexes, and phase separated protein states22. Biological complexity of the phase separated protein states23. Protein structure-function continuum