Small-Molecule Binding to Intrinsically Disordered Proteins - Characterization and Implications for Drug Design

Explore the fascinating world of intrinsically disordered proteins in this 19-minute Lennard-Jones Centre discussion group seminar by Dr. Gabi Heller from the University of Cambridge. Delve into the challenges and importance of characterizing these highly prevalent biomolecules, which make up 30-40% of human proteins and play crucial roles in various biological processes. Learn about integrative methods combining molecular dynamics simulations with nuclear magnetic resonance spectroscopy to study the pathogenicity and druggability of disordered proteins. Discover recent work on the monomeric form of the amyloid-β peptide, associated with Alzheimer's disease, and the identification of a small, drug-like molecule that prevents its toxic aggregation. Gain insights into the dynamic binding interactions between small molecules and disordered proteins, potentially leading to improved drug design for targeting proteins implicated in numerous human diseases. The seminar covers topics such as disordered protein systems, NMR spectroscopy, all-atom molecular dynamic simulations, conformational entropy, and the dynamics of 10074-G5 binding.

Intro
Introducing disordered proteins
Disordered protein systems
Nuclear Magnetic Resonance Spectroscopy (NMR)
All-atom molecular dynamic simulations
Conformational entropy of the protein
Conformational entropy: 'entropic expansion
Limitations of simulations
Dynamics of 10074-G5 binding