Allostery in Drug Discovery

Project Information

ALLODD

Grant agreement ID: 956314

DOI

10.3030/956314

Project closed

EC signature date 28 May 2021

Start date 1 September 2021

End date 31 August 2025

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 3 627 680,76

EU contribution

€ 3 627 680,76

Coordinated by

IDRYMA IATROVIOLOGIKON EREUNON AKADEMIAS ATHINON
Greece

Periodic Reporting for period 2 - ALLODD (Allostery in Drug Discovery)

Reporting period: 2023-09-01 to 2025-08-31

Summary of the context and overall objectives of the project

Most current drugs are designed to bind directly to the primary active sites (also known as orthosteric sites) of their biological targets. Drug discovery mainly focuses on the modulation or inhibition of protein function through small molecules that bind to their primary active sites. However, protein function may also be regulated through drug binding to distant sites, known as allosteric sites. Allosteric modulators offer a powerful yet underexploited therapeutic approach. They can elicit a richer variety of biological responses and, since they target less conserved binding sites, higher selectivity and fewer adverse effects may be obtained.
Over the course of four years, ALLODD brought together 13 Beneficiaries and 11 Partner Organizations from Academia and Industry from 12 countries across Europe. The project developed new computational and experimental platforms to detect allosteric ligands and sites, optimize allosteric ligands, create open datasets and tools, and contribute to scientific knowledge through dissemination, communication, and outreach activities. It supported the training and career development of 14 ESRs on Allostery in Drug Discovery through secondments, training events and activities, mentoring, and interdisciplinary collaboration.
Overall, ALLODD has strengthened the scientific foundation and practical tools needed to make allosteric drug discovery a feasible approach in both academia and industry.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

ALLODD has pursued a comprehensive strategy to train a new generation of scientists in the field of allosteric drug discovery and to advance research on allosteric modulators.

Recruitment and Training of ESRs
All ESRs were recruited by the end of 2022. ESRs followed an interdisciplinary research and training programme based on their individual Career Development Plans (CDPs), which were updated throughout the project in collaboration with their supervisors.
Training activities included:
• Three Training Schools and Networking Meetings (Barcelona 2022, Budapest 2023, Urbino 2024), offering thematic workshops and transferable skills training
• Two major public conferences: “Allosterism and Drug Discovery” (Strasbourg, 2023) and the “European Conference on Allostery in Drug Discovery” (Athens, 2025), both open to external participants
• 20 scientific webinars
• Participation in scientific and public engagement events such as the European Researchers’ Night and multiple Open Science Days
• Monthly ALLODD Journal Club to strengthen their analytical and critical skills
• Enhancing their writing skills with Blog posts and Meeting Summaries
• Community outreach by creating Science Slam videos
• Lectures & Courses to learn transferable skills
• Secondments (see below)
All ESRs were recruited in a doctoral program.

Secondments
Secondments formed a key part of the training programme, allowing ESRs to gain experience in complementary host institutions across academia and industry.

Research Results and Tools
The project focused on 5 scientific objectives:
• Identification of allosteric pockets
• Identification of allosteric ligands
• Understanding allostery at the molecular level
• Understanding biological responses of allosteric ligands
• Building a theoretical framework for allosteric modulation and a platform for the discovery of allosteric drugs
The first year was dedicated to organising the ESR hiring process, developing in greater detail the ESR projects, and setting up the working infrastructures for the project.
In the next three years, ESRs worked on their research projects and finalized their doctoral work. This is evidenced by the successful completion and submission of all deliverables as well as their scientific output in many publications and participation in conferences. All ESRs will submit a PhD executive summary or their theses by the end of the ALLODD project.

ALLODD Events
The ALLODD consortium is acting at a multidisciplinary network level for achieving a collaborative training and research effort through a series of training schools for the ESRs as well as scientific consortium meetings, which enable the exchange of results and facilitate ESR training across ALLODD.
1) The first ALLODD Workshop & PhD Induction Course
2) The second ALLODD meeting, the 1st Training School & Networking Meeting
3) The third ALLODD meeting, "Allostery in drug discovery awareness event and Symposium" and Workshop
4) The fourth ALLODD meeting, the 2nd Training School & Networking Meeting
5) The fifth ALLODD meeting, the IPR Training for Researchers & ESR Presentations on the Progress of their Research
6) The sixth ALLODD meeting, the 3rd Training School & Networking Meeting
7) The seventh ALLODD event, the European Conference on Allostery in Drug Discovery
8) The eighth ALLODD event, the Final Networking Meeting

Outreach, Dissemination, and Communication
ALLODD developed a robust outreach, dissemination, and communication strategy, including:
• An ALLODD logo to maintain a cohesive and recognizable visual identity
• Communication materials in the form of a banner, poster, flyer, and infographic, all created in line with the ALLODD visual identity guidelines
• Yearly newsletters summarizing project milestones and updates
• A project website, updated regularly with news and publications
• Active social media presence (Twitter/X, LinkedIn)
• The ALLODD YouTube channel
• Participation in 16 open science events
• Blog posts, science slam videos, and science communication materials created by ESRs
• 4 Press releases
• 37 peer-reviewed publications have been produced (https://www.allodd-itn.eu/publications.html and https://zenodo.org/communities/allodd-itn)
• 50 Conference presentations

Exploitation and Sustainability
The consortium has identified the following Key Exploitable Results (KERs):
KER1: Platform for detecting allosteric ligands
KER2: Predictive web-based tool for identifying allosteric pockets and networks in proteins
KER3: Validated experimental pipelines for detecting allosteric modulators
KER4: Dataset of allosteric site predictions and ligand annotations
KER5: Curated database of experimental allosteric ligands and sites
KER6: ALLODD Webinar Series & YouTube Knowledge Base
KER7: Ligand for DC-SIGN expressing cells for targeted delivery of therapeutics

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

• Novel computational tools have been developed for identifying cryptic and allosteric pockets and networks in proteins
• Experimental workflows, including cryo-EM and proteomics, have been validated for the detection of allosteric targets
• New datasets for allosteric site predictions and ligand annotations are being compiled and released via open-access repositories
• Several ESR-led studies have provided new insights into allosteric modulation of GPCRs and kinases—systems with major therapeutic relevance
• Allosteric ligand optimization with computational and experimental approaches
• Enhancing European excellence in pharmaceutical research and innovation
• Training 14 highly skilled ESRs across academia and industry, creating a new generation of scientists equipped to address current and future biomedical challenges
• Fostering cross-sectoral collaborations and strengthening the European Research Area through shared tools, secondments, and joint publications
• Promoting open science, public engagement, and transparent communication of research through webinars, videos, blog posts, and outreach activities

ALLODD Events and Workshops

ALLODD Management and Governing Bodies Scheme

ALLODD Training Activities

ALLODD Consortium