Projektbeschreibung
Einblicke in die Konformationsänderungen von Proteinen in ihrer Funktion
Die Funktion von Proteinen hängt von dynamischen Veränderungen ihrer dreidimensionalen Konformationen und von dynamischen Wechselwirkungen mit anderen Molekülen ab. Das derzeitige Wissen über die Proteinstruktur stammt hauptsächlich aus Experimenten, die Schnappschüsse einzelner Proteinzustände bieten. Das vom Europäischen Forschungsrat finanzierte Projekt DynaPLIX wird Methoden ausarbeiten, mit denen die Bewegungen von Proteinen untersucht werden können, während sie ihre Funktion erfüllen. Das Projekt wird den dynamischen Prozess der Ligandenbindung an Proteine aus einer Perspektive enthüllen, die Struktur, Kinetik und Thermodynamik einbezieht. Angesichts der kommerziellen Bedeutung von Proteinen werden die erarbeiteten Methoden dazu beitragen, industrielle und medizinische Anwendungen von Proteinen zu fördern.
Ziel
Proteins are biological macromolecules that are vital to all processes of life. Understanding the functions of proteins has great scientific and commercial value: proteins are used as industrial enzymes, as pharmaceutical treatments, and many proteins are the targets of drugs. Current knowledge of protein function is primarily based on static structures, which have provided great insights about structure-function relationships that today form the basis for protein science and protein engineering. Proteins are, however, not static molecules, but undergo spontaneous transitions between alternative structural states, some of which are rare, transient conformations that are essentially invisible to traditional methods. These dynamical properties are known to be critically important for function, but high-resolution studies of dynamics have so far been conducted merely as an “add-on” following structural studies. To change the situation, we aim to establish “integrative biomolecular dynamics” by developing methods that integrate time-resolved X-ray crystallography, nuclear magnetic resonance spectroscopy, and molecular simulations to study the motions of proteins while they carry out their function. We focus on the challenging problem of molecular recognition because it represents a poorly understood frontier in molecular science where advances are expected to have great impact. Specifically, we will address the question of how proteins bind ligands by describing with atomic resolution the entire dynamic process to reach a consistent kinetic, thermodynamic, and structural view. We are at a point where it will be possible to develop the individual techniques required for our integrative biomolecular dynamics approach. As a team we can leverage ongoing developments in hardware and methods, while ensuring the tight integration between methods that is needed to study complex dynamical systems. We thus aim to move structural biology into a new era of protein dynamics.
Wissenschaftliches Gebiet
- natural sciencesearth and related environmental sciencesgeologymineralogycrystallography
- natural sciencesmathematicsapplied mathematicsdynamical systems
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
- natural sciencesbiological sciencesmolecular biologystructural biology
- natural sciencesphysical sciencesopticsspectroscopy
Schlüsselbegriffe
Programm/Programme
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Thema/Themen
Finanzierungsplan
ERC-SYG - ERC-SYGGastgebende Einrichtung
22100 Lund
Schweden