Understanding and designing substrate specificity of methyltransferases by molecular dynamics simulations and experiment

Protein lysine methylation is a post-translational modification which is introduced by protein lysine methyltransferases (PKMTs). Currently the rules determining the substrate selection of PKMTs are not well understood. The Jeltsch group has developed a unique and powerful approach to study PKMT specificity based on peptide SPOT synthesis, which we aim to apply here to novel PKMTs. In collaboration with the Jeltsch group, we conduct large-scale MD simulations of PKMT-peptide complexes to understand the experimental data in the context of available protein structural data, This will lead to the identification of critical contacts which afterwards will be studied experimentally. Our project will include advanced questions like the investigation of coupled interactions, binding of novel and optimized substrates and the analysis of the effects of somatic mutations in PKMTs observed in cancer cells. The project will adapt and currently established workflows to perform and analyse of many hundred simulations and report the simulation results and further develop data management and data structure.

This research project is funded in the framework of the Stuttgart Cluster of Excellence SimTech.


Philipp Schnee



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