This course explores a new phase in structural biology, focusing on studying proteins in the vapour phase. The learning outcomes include understanding the importance of protein shape in human health and drug development, as well as gaining insights into dynamic interactions between proteins, lipids, and drugs. The course teaches skills such as using mass spectrometry as an analytical tool, identifying building blocks within complexes, and monitoring protein unfolding. The teaching method involves lectures and discussions on topics such as the mass spectrum of various molecules, mechanisms of drug resistance, and the impact of drug binding on protein processing. The intended audience includes students and professionals in the fields of chemistry, biology, biochemistry, and pharmaceuticals who are interested in cutting-edge research in structural biology.
Overview
Syllabus
Intro
Count Rumford one of the founding members of the Royal Institution
J.J. Thomson unveiled the discovery of the electron
First mass spectrometers
Mass spectrum of aspirin
Mass Spectrum of Melanocyte Stimulating Hormone
Nobel prize for chemistry 2002
Electrospray - without unfolding
Folding in the presence of molecular chaperones
A new phase for structural biology?
Proteins with many different conformations
The passage of complexes through the mass spectrometer
Scientific goals and questions
Unraveling polydispersity - the alpha crystallins
Disassembly predicts evolutionary assembly pathways
Mass spectrometry to identify the building blocks within complexes
Micelles protect membrane complexes and lipid binding remains intact
From micelles to membrane proteins in the gas phase
ATP Synthase - 95:1 DDM: protein
Mass spectrum of intact ATPase from Thermus thermophilus
Mass spectral assignment strategy - Massign
New ways to study how small molecules stabilise membrane proteins
Monitoring unfolding of AqpZ as a function of POPG binding
P-glycoprotein - an ABC transporter and drug efflux pump
Looking for a small difference
Mechanisms of drug resistance
Zinc binding to a human metalloprotease ZMPSTE24
Progeria is a common side effect of anti- HIV drugs
Processing of lamin A peptides is inhibited by drug binding
Sugar transporter semiSWEET - remodeling the lipid bilayer
From Neon to rotary motors to flipping lipids and drugs
Taught by
The Royal Institution
