Project description
Implicit transfer operators support fast, general and scalable protein simulations
A single amino acid substitution or a slight conformational change can significantly alter a protein’s function. Modelling such minute changes and their dynamic functional effects would revolutionise rational protein engineering for fields from energy to biomedicine. The ERC-funded SPETITO project aims to optimise its modelling platform – capable of simulations 100 000 times faster than conventional molecular dynamics simulations – to make it applicable to all molecular systems and scalable to larger molecules. Work will include developing a transferable ‘implicit transfer operator’ model capturing universal protein physics at microsecond-scale, a protein sequence gradient-based optimisation framework to efficiently explore sequence space and an automated thermodynamics-integrated design pipeline to engineer tailored proteins.
Objective
Minute changes in proteins—such as a single amino acid substitution—can profoundly impact cellular function. A computational model capable of systematically mapping the relationship between protein sequences, their dynamics, and their interactions with other biomolecules would revolutionize biology and enable rational, physics-informed bioengineering applications. SPETITO outlines the methodological foundations for such a framework.
Recent advances in deep generative AI (GenAI) have enabled surrogate methods for efficient molecular dynamics (MD) simulations, tackling the challenge of sampling rare events and conformational transitions. The PI co-developed groundbreaking methods—Boltzmann Generators (BG) and Implicit Transfer Operators (ITO)— that enable the study of conformational changes, protein folding, and prediction of experiments five orders of magnitude faster than MD.
However, these methods cannot generalize across molecular systems nor scale to larger molecules, severely
limiting their utility. To address this, we propose developing and disseminating transformative technologies
through widely accessible software:
• A transferable ITO (TransITO) model that captures universal protein physics, enabling rapid sampling
with microsecond-time-steps for any protein system without requiring system-specific training data.
• A ‘protein sequence gradient’-based optimization framework, enabling efficient exploration and optimization of protein sequence space for targeted functional outcomes.
• An automated protocol for protein design that integrates multiple thermodynamic constraints, facilitating the rational engineering of proteins with desired properties.
Beyond turbo-charged atomic-resolution insights into biophysics, TransITO will enable rational, physics-informed protein engineering. With experimental collaborators, we will apply TransITO to vaccine development, to accelerate therapeutic design for infectious diseases.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
This project's classification has been human-validated.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
This project's classification has been human-validated.
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences computer and information sciences computational science
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
- natural sciences biological sciences biophysics
- natural sciences computer and information sciences artificial intelligence machine learning
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2025-COG
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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.
412 96 Goteborg
Sweden
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