Stochastic thermodynamics of biochemical replication

Información del proyecto

STBR

Identificador del acuerdo de subvención: 101104602

DOI

10.3030/101104602

Proyecto cerrado

Fecha de la firma de la CE 16 Marzo 2023

Fecha de inicio 1 Mayo 2023

Fecha de finalización 30 Abril 2025

Financiado con arreglo a

• Marie Skłodowska-Curie Actions (MSCA)

Coste total

Sin datos

Aportación de la UE

€ 230 774,40

Coordinado por

KOBENHAVNS UNIVERSITET
Denmark

Objetivo

The main goal of this project will be to construct a thermodynamically consistent comprehensive model for biochemical replication using stochastic thermodynamics and control theory.

I will subjugate the process of kinetic proofreading (KPR) to several thermodynamic bounds that have recently been discovered, in order to study the thermodynamic performance of this process. This will be done by considering the process as a chemical reaction network where a sequence of irreversible steps consume energy to increase replication accuracy and are hence bounded by fundamental no-go theorems such as the thermodynamic uncertainty relation (TUR) or the thermodynamic speed limit (TSL). I then investigate how the topology and reaction rates of the KPR network can be optimized with respect to error rate and dissipation by means of machine learning, to deduce how close biological systems operate to these bounds. Subsequently, I will extend the results to the conformational proofreading (CPR) process, where an energy handicap is added to the free energy to increase binding specificity at the expense of binding affinity. The CPR is a proofreading scheme that does not consume energy by burning ATP/GTP, so the entropy production has its origin in the conformational change.

Finally, I test the robustness of the aforementioned KPR and CPR networks. In realistic systems, the kinetic rates can fluctuate as a consequence of e.g. temperature or chemical density variations, which can possibly destabilize the network and lead to more errors in the replication process. This will be done by considering the networks as input-output systems that can be studied by control theory. This provides fundamental bounds such as Bode's sensitivity integral to complement the TUR and TSL.

I expect that the research results will lead to a better understanding of the fundamental limits on error correction in biological systems and will inspire further research in biophysics and structural biology.

Ámbito científico (EuroSciVoc)

• ciencias naturales › ciencias físicas › termodinámica
• ciencias naturales › matemáticas › matemáticas puras › topología
• ciencias naturales › ciencias biológicas › biofísica
• ciencias naturales › informática y ciencias de la información › software › software de aplicación › software de simulación

Palabras clave

• Stochastic thermodynamics
• kinetic proofreading
• conformational proofreading
• control theory

Programa(s)

• HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) PROGRAMA PRINCIPAL
  

Tema(s)

• HORIZON-MSCA-2022-PF-01-01 - MSCA Postdoctoral Fellowships 2022
  

Régimen de financiación

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

Convocatoria de propuestas

HORIZON-MSCA-2022-PF-01

Coordinador

KOBENHAVNS UNIVERSITET

• Aportación neta de la UEn: € 230 774,40
• Dirección: NORREGADE 10 ; 1165 KOBENHAVN ; Dinamarca
• Región: Danmark › Hovedstaden › Byen København
• Tipo de actividad: Higher or Secondary Education Establishments
• Coste total: Sin datos