Our research paper on predicting the interactions between glycolytic enzymes within a human cancer cell environment is now published in PNAS! The paper highlights the successful application of the first atomic-scale model of a human cell segment to study life-sustaining processes hidden within cells. Functional interactions of enzymes are often influenced by the crowded and complex cell environment surrounding them. Using classical molecular dynamics methods to simulate a segment of the cell cytoplasm environment, we predicted the mechanisms of these enzyme interactions at high spatiotemporal resolutions (beyond current experimental capabilities). The three enzymes (PGK, GAPDH, PGM) we examined were seen communicating via specific sticky patches on their surfaces, with the patches often occurring in the region of enzyme active sites. Force-field benchmarking further highlighted the important role of water in facilitating these enzyme-enzyme interactions.

Using the sticky patches, the enzymes were seen organizing into structures resembling “metabolons”- dynamic metabolic enzyme complexes. Such complexes are known to occur experimentally and facilitate metabolic pathways’ efficacy. Glycolytic metabolons have been associated with cancer cells by other experimental groups.

www.pnas.org/doi/abs/10.1073/pnas.2414206122