Understanding Peripheral Protein-Membrane Interactions: Membrane Recognition, Dynamics, Function and Therapeutic Opportunities
Membrane proteins are integral to signal transduction and many other critical cellular processes. Peripheral membrane proteins (PMPs) are a class of membrane proteins that attach to the lipid bilayer, acting on the lipid-water interface, in contrast to transmembrane proteins, which are fully embedded in the cell membrane. While peripheral membrane proteins comprise a significant percentage of all membrane proteins, they have not been extensively studied possibly due to the complexity of the protein-membrane interface and the limited number of structural studies of protein-membrane binding. For example, the known K-RAS and PI3Kα oncogenes, two of the most prevalent protein drug targets in cancer, and α-synuclein a major target in Parkinson’s disease still lack FDA-approved drugs. This conference will focus on the experimental as well as computational advances on PMP studies; the interaction of membrane peripheral proteins with membranes and with other membrane proteins- for example cytoskeletal proteins, their role in cell biology in health and disease, targeting PMPs for drug design.
Although PMPs are important for several cellular functions for various functions, little is known about their mechanism of function because they only bind transiently to a membrane, making it difficult to assess binding conformations as they can be found in states attached to the membrane as well as completely solvated in water. This poses many challenges for experimental as well as the computational studies to elucidate specific details of their function of these systems, which have to follow this non-equilibrium process. This workshop intends to discuss this relatively overlooked research area by inviting computational experts to discuss non-equilibrium methods used to study the transient states of membrane proteins as well as machine learning to study the protein-membrane interface, and experimentalists on specialized techniques for studying PMPs such as SPR, NMR, FRET, secondary ion mass spectrometry.
Moreover, we plan to discuss re-considering the accessibility of membrane-protein interfaces by drug-like molecules, which has been so far unexplored, possibly due to the complexity of the interface and the limited number of structural studies of protein-membrane binding. The advantages of discussing targeting peripheral membrane proteins in drug design are two-fold: a) it will target peripheral membrane proteins that currently remain undruggable as protein-membrane interactions are believed to be inaccessible to drug-like molecules, b) it will enhance drug selectivity and modulatory control of proteins since allosteric inhibitors do not bind to the protein active site.
Zoe Cournia (Biomedical Research Foundation) - Organiser
Matthias Buck (Case Western Reserve University, Cleveland Ohio) - Organiser
Alemayehu Gorfe (Medical School, University of Texas at Houston) - Organiser