The applicant has extensive experience in the development of predictors for posttranslational protein modifications at the sequence level and would like to expand his work to directly include structural information.
The host laboratory offers the method FoldX that can fast and reliably predict the effect of sequence variation on protein interactions at the structural level, such as the fitting of different substrate peptides into the binding pocket of a modifying enzyme.
The anticipated project comprises
- improvement of the FoldX force field to include model systems of posttranslational modifications (PTMs),
- the sampling of valid substrate sequence motifs for selected PTMs and exertion of derived sequence sets to improve or de novo construct predictor s to find previously unknown substrates for these PTMs. This includes
- the investigation of taxon-dependent substrate specificities and is especially useful
- for examples where the limited number of known substrates has previously prohibited the development of predictors. Furthermore,
- the effect of naturally occurring mutations at or around known PTM sites will be analyzed and discussed in the context of disease conditions and
- the impact of the PTM itself on the structure of the modified protein will be studied. Finally,
- the approach can be extended to the more general scheme of peptide/protein interactions also for non-PTM examples.
Fields of science
- medical and health sciencesbasic medicineneurologydementiaalzheimer
- natural sciencesbiological sciencesgeneticsmutation
- medical and health sciencesbasic medicineneurologyparkinson
- natural sciencesbiological sciencesgeneticsgenomes
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
Call for proposal
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