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Structural biology relates to the study of the structure of molecules and macromolecules and how they fold. It is also concerns the structural modifications that can affect their function. Proteins and nucleic acids adopt a specific three-dimensional structure (also called tertiary structure) that depends on their basic composition (primary structure). It is essential to study the structure of these molecules that lie at the heart of biological processes to better understand how they perform their functions. This is the primary purpose of structural biology.

By studying the structure of molecules, it is possible to understand how they function. The comparison of their physiological structure with poorly conformed structures allows us to better understand certain diseases. Indeed, un protein misfolding can be the cause of diseases such as Alzheimer’s, Parkinson’s or cystic fibrosis. The knowledge acquired through structural biology can play a key role in the development of new treatments.

Structural biology analyses are performed using imaging techniques such as cryo-electron microscopy (cryo-EM), X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy. These techniques allow the observation of isolated molecules but also of larger structures such as molecular complexes (notably the association of proteins and/or nucleic acids forming a functional unit), viruses and organelles.

Structural biology has been used for many years. In particular, in 1953, it enabled the determination of the structure of DNA using X-ray diffraction. And more recently, the resolution of the structure of the Spike protein of the SARS-CoV2 virus allowed researchers to better understand the fusion mechanism of the virus and to study the interactions brought into play by neutralizing antibodies during infection or vaccination.

This constantly evolving field now allows us to solve more and more precise structures, to study larger and larger molecular complexes and to study processes that occur in less than a tenth of a trillionth of a second. Computational models, complementary to structure resolution methods, allow the design of new proteins not found in nature. These new proteins with useful functions may lead to potentially life-saving drugs.

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Alzheimer's association - Richard C. Mohs,Nigel H. Greig

Drug discovery and development: Role of basic biological research

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