Chemical biology studies of protein-lipid interactions
- Reference number
- MDB09-0010
- Start and end dates
- 090801-131231
- Amount granted
- 2 100 000 SEK
- Administrative organization
- Stockholm University
- Research area
- Life Sciences
Summary
The project aims to combine (i) an in vitro transcription/translation system, developed by the Swedish partner, that makes it possible to measure the free energy of interaction between amino acids incorporated into a transmembrane alpha-helix and the endoplasmic reticulum membrane, with (ii) the novel Flexizyme technique developed by the Japanese partner that allows an essentially unlimited variation of non-proteinogenic synthetic amino acids to be charged onto a suppressor tRNA. By using the charged suppressor tRNA to suppress a stop codon engineered into a defined position within the part of the gene that encodes the transmembrane helix, the non-proteinogenic amino acid can be incorporated at will and its effect on membrane integration of the helix can be measured in a true biological context. We will explore a wide range of side-chain structures in an attempt to develop a fragment-based free energy scale that describes the membrane affinity of different kinds of groups found in drug-like molecules and that can illuminate the interaction energetics between biomolecules and the endoplasmic reticulum membrane.
Popular science description
Projektet syftar till att kombinera tekniker utvecklade av den svenska respektive japanska partnern för att studera hur olika slags molekyler binder till biologiska membran. Projektet har relevans för både läkemedelsutveckling och biologisk grundforskning.