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The Fluctuating Enzyme: From Catalysis to Vibrational Dynamics

Descrizione del progetto

Comprensione della natura stocastica della catalisi enzimatica

Gli enzimi sono catalizzatori centrali per i processi biologici essenziali che governano la crescita, lo sviluppo e il metabolismo di tutti gli organismi viventi. Alcune tecnologie d’avanguardia hanno consentito agli scienziati di caratterizzare e manipolare gli enzimi, fornendo preziose informazioni riguardo le reazioni enzimatiche a livello della singola molecola. Il progetto FLUCTENZ, finanziato dall’UE, si concentrerà sulla natura stocastica dell’attività enzimatica, in particolare quando gli enzimi sono sottoposti a fluttuazioni termali. A tal fine, alcuni scienziati svilupperanno metodi teorici e strumenti matematici che li aiuteranno a comprendere e determinare i principi del comportamento enzimatico in diverse condizioni. Considerando che la catalisi enzimatica è la forza trainante della vita così come la conosciamo, i risultati del progetto avranno una notevole importanza per la scienza di base e per quella applicata.

Obiettivo

Enzymes spin the wheel of life by catalyzing a myriad of chemical reactions central to the growth, development, and metabolism of all living organisms. Without enzymes, essential processes would progress so slowly that life would virtually grind to a halt, and the quest to determine their inner workings thus continues to attract and fascinate scientists over a broad range of disciplines. Cutting-edge methods now allow one to observe and manipulate individual enzymes in their reaction course. These revealed that chemistry at the single-molecule level is inherently stochastic and, at times, extremely unintuitive. Thermal fluctuations push enzymes to vibrate erratically and force a probabilistic description, but classical approaches are deeply entrenched in determinism, and so is our basic expectation for how things should behave in the world around us. The groundbreaking purpose of this proposal is to bring advanced theoretical methods and mathematical tools to the analysis of stochastic fluctuations of enzymes and proteins at the single-molecule level. These will be based on state-of-the-art approaches in statistical physics and stochastic processes that I will adapt and further advance to need. Equipped with mathematical techniques that have so far been foreign to the field, I expect to rectify fundamental flaws in our understanding, predict the emergence of novel phenomena, and show how single-molecule fluctuations can be extracted from bulk, steady-state, concentrations—despite belief that this is fundamentally impossible. Novel analysis methods that I will apply to tens of thousands of protein structures would complement these efforts and aid in the discovery of unifying principles governing thermal fluctuations of enzymes and proteins. The amalgamation of all these efforts will pave the way to large-scale, multi-tier, characterization of fluctuations which is expected to transform our understanding of enzymes and enzymatic catalysis.

Meccanismo di finanziamento

ERC-STG - Starting Grant

Istituzione ospitante

TEL AVIV UNIVERSITY
Contribution nette de l'UE
€ 1 496 875,00
Indirizzo
RAMAT AVIV
69978 Tel Aviv
Israele

Mostra sulla mappa

Tipo di attività
Higher or Secondary Education Establishments
Collegamenti
Costo totale
€ 1 496 875,00

Beneficiari (1)