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Memory dependent PAth Sampling methods for understanding long TIMEscale molecular processes

Project description

Understanding time in chemistry

Chemical processes and chemistry play a vital role in numerous industries, innovations, and the development of novel tools and technologies. These advancements are essential for addressing the challenges posed by climate change. Regrettably, the significance of time in chemistry has often been overlooked, leading to inefficiencies in simulations and research. In this context, the ERC-funded PASTIME project aims to establish a methodological framework for effectively incorporating and understanding the role of time in chemistry. The project’s objective is to create a memory-dependent transition interface path sampling technique for chemical modelling. This innovation holds the potential to revolutionise chemical simulations.

Objective

Time matters: timescales determine the fate, behavior and functionality of living matter. Especially the interplay between fast and slow molecular processes is omnipresent in biochemistry (protein folding, enzymatic conversions, molecular signaling, etc.). However, in chemistry, models are lacking to properly understand time and its effect on this difficult biological reality.

PASTIME will lay the methodological foundations for a correct understanding of time in chemistry by introducing memory dependent transition interface path sampling to chemical modeling. We will tune the memory that is kept in simulations by creating new path ensemble definitions. The problem will be made computationally solvable by cutting molecules' pathways short. Long timescale effects will be studied through pathway statistics. We will achieve higher decorrelation in the sampling by designing new Monte Carlo moves in path space, such as alchemical moves that change the identity of atoms on the fly, and smart use of memory expansion with a replica exchange move. These new time concepts will be challenged and experimentally validated in a context of drug transport kinetics: drug (un)binding to protein binding sites, and permeation of molecules through cell membranes. The modeling principles will be converted to new algorithms that are computationally feasible today and will be shared in open software.

With PASTIME we will be able to understand slow time effects in molecular interactions. Appropriate memory reduction and tuning will give us the methods to understand time in an endless range of molecular processes, and this work will contribute to drug design, biochemistry, physiology, catalysis, material and polymer science.

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2022-COG

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Host institution

UNIVERSITEIT GENT
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 000 000,00
Address
SINT PIETERSNIEUWSTRAAT 25
9000 GENT
Belgium

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Region
Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 000 000,00

Beneficiaries (1)

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