Molecular Dynamics Simulations of the Substrate Recognition of Protein Lysine Methyltransferases

Protein lysine methylation is a post-translational modification which is introduced by Protein Ly-sine methyltransferases (PKMTs). Currently the rules determining the substrate selection of PKMTs are not well understood. The Jeltsch group has developed a unique and powerful ap-proach to study PKMT specificity based on peptide SPOT synthesis, which we aim to apply here to novel PKMTs. To understand the experimental data in the context of available protein structural data, we will to conduct high-end MD simulations of PKMT-peptide complexes. 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.