The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) serves as a global archive for the three-dimensional (3D) shapes of biological molecules. Established in 1971, it functions as a central resource for scientific research and education. The PDB provides access to atomic-level 3D structures, which are used to understand how biological systems operate.
The Three-Dimensional World of Molecules
The PDB archives 3D structural data for biological macromolecules, including proteins, DNA, RNA, and their complex assemblies. These molecules are life’s fundamental machinery, performing nearly all cellular functions. Their specific 3D arrangement is paramount to their function, much like a precisely shaped key fits into a specific lock.
The sequence of amino acids in a protein dictates its unique 3D folded shape. Even slight alterations, such as a change in a single amino acid, can significantly modify or disable a molecule’s role, potentially leading to diseases like sickle cell anemia or cystic fibrosis. Proteins, for instance, can act as structural components, enzymes that speed up reactions, transporters, or signaling molecules, all dependent on their precise architecture.
Understanding Health and Disease
Scientists utilize the 3D structures within the PDB to unravel the molecular mechanisms underlying diseases. For example, understanding how a virus infects a cell or an enzyme malfunctions involves studying the specific shapes of the molecules. This structural information allowed for the development of HIV protease inhibitors, a class of drugs that revolutionized HIV/AIDS treatment, by targeting the HIV protease enzyme’s shape.
The PDB plays a significant role in drug discovery and development. Knowing the precise 3D shape of a disease-related molecule, such as an enzyme or receptor, enables researchers to design drugs that specifically bind to and either activate or block its function. This approach, known as structure-based drug design, has facilitated the discovery of approximately 90% of new drugs approved by the US Food and Drug Administration between 2010 and 2016. The database also contributes to biotechnology, supporting the engineering of enzymes for various industrial applications.
Revealing Molecular Shapes
The 3D structures in the PDB are primarily determined using advanced experimental techniques. X-ray crystallography is the most common method, accounting for the majority of structures, though its proportion has declined. This technique involves crystallizing the molecule and exposing it to X-rays to generate a diffraction pattern, which deduces the atomic arrangement.
Nuclear Magnetic Resonance (NMR) spectroscopy is another technique, useful for studying smaller proteins and their dynamics in solution. Cryo-electron microscopy (Cryo-EM) has seen a significant increase in contributions, especially since 2015, now accounting for up to 40% of new structure deposits. These methods provide the atomic-level detail necessary for populating the PDB archive.
Exploring the Database
The PDB is a public, open-access resource, allowing anyone to access and visualize molecular structures. Researchers, students, and the general public can explore the database using online tools provided by the RCSB PDB website. This accessibility supports a wide range of users, from those studying fundamental biology to those interested in specific disease mechanisms.
By making structural data freely available and searchable, the PDB fosters global scientific collaboration and accelerates discovery. It integrates data with over 40 external biological data resources, offering comprehensive insights into molecular function and disease. Educational resources, such as the “Molecule of the Month” series, support learning and understanding of structural biology for diverse audiences.