Drug discovery with AlphaFold and Flow matching

What do I find in this text?

• Why are proteins essential for drug discovery?
• What is the structure of proteins?
• What are intrinsically disordered proteins and ensembles of structures?
• Which experimental and computational methods exist to determine and predict the structure of proteins?
• What is AlphaFold, and why is it essential for drug discovery?
• What are the limitations of AlphaFold in drug discovery?
• Which methods exist to determine structural ensembles?
• What is flow matching, and how do you make protein ensemble predictions?
• What is AlphaFlow, and how does it compare to Molecular Dynamics simulations?

Note: While all these questions are answered in this text, the focus is on the last two questions and their corresponding tools. The background of all questions will be detailed later and linked here.

Structure of proteins

Proteins adopt three-dimensional structures in solution. The structure of a protein determines its biological function and interactions with other molecules, including drugs. Typical drug molecules are antibodies, nanobodies, or small molecules. The interaction of those drugs with the protein is vital for the protein's function in a given environment.