AI-assisted protein-protein interaction interface clustering and discovery of novel modes of protein binding
Supervision
Katja Luck
IMB, 1st Supervisor
Pedro Beltrao
ETHZ, 2nd Supervisor
Objectives
Build AI-based routines that use biophysical properties and topology to compute protein-protein interaction (PPI) interface similarities; Build routines enabling improved protein complex structure prediction; Apply routines to discover novel modes of protein-protein binding.
Methodology
We build upon existing expertise and routines in the lab in protein complex structure prediction and PPI interface similarity computations to bring methods to the next level in terms of sensitivity and specificity. To this end, we will use AI-based representation of PPI interface structure and AI-based tools for protein structure prediction. We will leverage published and unpublished datasets of experimentally resolved and predicted protein complex structures to discover novel modes of protein-protein binding.
Required skills
Interest in integrative structural biology and structural computational biology
Good basics in coding, preferentially python
Interest in protein science and in AI approaches to structural biology.
Planned Secondments
Host: ETHZ (P. Beltrao), Duration: 2 Months; When: Year 1, Goal: Aid in ultrafast clustering of structural data.
Host: CNRS (I. Bludau), Duration: 1 Month, When: Year2, Goal: Experimental analysis of protein structures with mass spectrometry
Host: BIOCEV (P.Novák), Duration: 1 Month; When: Year 3, Goal: Use of structural proteomics to explore predicted protein interaction interfaces.
Enrolment in doctoral programs
Host institute’s International PhD program.
Registration upon acceptance at Johannes Gutenberg University in Mainz
Project specific requirements
If you are interested in this project, please also apply to the current International PhD program (IPP) call of the host institute, which closes October 16th at noon CEST. This project has also been advertised there. PhD students can only be admitted at the host institute, if they passed the IPP selection process. The next call will only open in Spring 2026. In case you are interested in this project but missed the IPP deadline (October 16th), please contact the recruiting group leader asap.
References
1 Lee et al MSB 2024 “Systematic discovery of protein interaction interfaces using AlphaFold and experimental validation”
2 Strom and Luck Curr Op Str Biol 2025 “Bias in, bias out – AlphaFold-Multimer and the structural complexity of protein interfaces”
3 Hubrich et al BioRxiv 2025 “Variant characterization in the intrinsically disordered human proteome”