Postdoc kinase affinity modelling using synthetic data

Are you a highly motivated, ambitious Postdoc candidate interested in pursuing cutting-edge artificial intelligence research in the area of computational medicinal chemistry? Are you interested in building better models to predict the properties of the next cancer therapeutics?
We have an opening for a Postdoctoral Researcher at the Molecular Physiology research group (MolPhys) with dr. Anthe Janssen in the Leiden Institute of Chemistry (LIC).

Main goal
Develop statistical AI models to predict binding affinities for as many kinases as possible based on docking experiments.

Previously, we have created a large dataset of experimentally determined kinase-ligand pairs, and generated 3D complexes for all measurements using open-source molecular docking software. In this project, we aim to expand on this idea by partnering with Dompé farmaceutici S.p.A. They have developed the Exscalate virtual screening platform, which allows molecular docking at an unprecedented throughput. This will enable us to dock all possible kinase-ligand combinations, around 108 complexes. We will further push to expand the coverage of the kinases included, using both Dompé’s in house and yet to generate homology models to approach 100% kinome coverage (previous work reached around 40%).
The newly generated dataset of 3D poses, apart from being released to the community, will be used to develop AI models to predict binding affinities. These will be trained on the ± 350,000 literature affinity values aggregated previously. Pose selection by an in house developed AI model of Dompé will be tested to assess the impact on performance. As pose encoding, various interaction fingerprints will be assessed, as well as other molecular descriptors such as DompeKeys. With validated models, we will generate the first-of-its-kind full matrix of predictions for all ligands against all kinase targets. If time and resources permit, other docking engines such as Uni-mol v2.0 will be used to broaden the benchmarks, and we will explore possible validation of this generated matrix by performing Absolute Free Energy (ABFE) calculations on a stringent selection of relevant new datapoints.

Work and profile

Key responsibilities

• Generating large scale molecular docking datasets for artificial intelligence training
• Experiment design & Data management
• Publication in high-quality journals
• Disseminating results in conferences

Essential Selection Criteria

• PhD degree in the area of medicinal computational chemistry
• Strong experience in at least one of the following: molecular docking; training and using artificial intelligence models
• Motivated to conduct independent computational research
• Good communication skills, ability and willingness to work in a team

About Us
The Molecular Physiology group is an interdisciplinary group at the Leiden Institute of Chemistry, Leiden University. The artificial intelligence research is led by dr. Anthe Janssen. Please find more details here https://www.janssenlab.nl/.

What’s in it for you?

• Opportunity to grow your independent research vision
• Collaborative project with an industrial partner
• Infrastructural support to pursue ambitious research directions

Application process
Please submit your application via the online recruitment system, via the blue button at the top or bottom of this page. Please ensure that you upload the following documents in PDF:

• A letter of motivation
• CV (contact of at least two references, maximum of three references)
• A document describing your fit to the selection criteria

Description of organisation and terms of employment
We start reviewing applications immediately and until the position is filled. We offer a position for 12 months. You will be appointed in accordance with the Collective Labour Agreement for Dutch Universities. The salary range is from € 3.378 - € 5.331 gross per month, based on a full-time appointment (pay scale 10 in accordance with the Collective Labour Agreement for Dutch Universities).

Leiden University offers an attractive benefits package with additional holiday (8%) and end-of-year bonuses (8.3 %), training and career development. Our individual choices model gives you some freedom to assemble your own set of terms and conditions. For international spouses we have set up a dual career programme. Candidates from outside the Netherlands may be eligible for a substantial tax break. For more information, see the website.

Faculty
The Faculty of Science at Leiden University is a world-class faculty where staff and students work together in a dynamic international environment. It is a faculty where personal and academic development are top priorities. Our people are committed to expand fundamental knowledge by curiosity and to look beyond the borders of their own discipline; their aim is to benefit science, and to make a contribution to addressing the major societal challenges of the future.

The research carried out at the Faculty of Science is very diverse, ranging from mathematics, information science, astronomy, physics, chemistry and bio-pharmaceutical sciences to biology and environmental sciences. The research activities are organized in eight institutes. These institutes offer eight bachelors’ and twelve master’s programmes. The faculty has grown strongly in recent years and now has more than 2,300 staff and over 5,000 students. We are located at the heart of Leiden’s Bio Science Park, one of Europe’s biggest science parks, where university and business life come together.

University
Leiden University is one of Europe’s leading international research universities.

Thanks to its committed and inspired employees, the university enjoys a leading role in academic research and education. Leiden also scores very well every year in prominent rankings. This means that, to maintain our position, the bar is set very high. Regardless of the work you do at our university, you are always encouraged to broaden your horizons, develop your talents and reach your full potential. Will you become our newest colleague?

Do you have questions about this position? Please contact Jessica van Krimpen-Kraaijenoord, management assistant, j.e.van.krimpen@lic.leidenuniv.nl, +31 71 527 5782.

You can find more information about the faculty of Science at https://www.universiteitleiden.nl/en/science/about-faculty-of-science. For more information about working at Leiden university please visit https://www.universiteitleiden.nl/en/working-at.

Are you enthusiastic about this vacancy? We are looking forward to get to know you. You can apply until March 1st, 2025, using the application button below.

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