Post-translational modifications in protein-protein interactions

Protein-protein interactions are rarely regulated by a single post-translational modification in isolation — in reality, combinations of PTMs act together, often non-additively, to fine-tune whether, how strongly, and when two proteins bind. Yet most structural and computational studies still treat PTMs one at a time, leaving the combinatorial logic of multi-site modification largely unmapped. In this project, we aim to use molecular dynamics simulations to characterize how combinations of PTMs reshape the structural and dynamic landscape of protein-protein interfaces — including allosteric, distal effects — and to combine these simulations with machine learning to predict how a given PTM combination will affect binding affinity and specificity.