This project builds on pioneering research into lipid mediators, including leukotrienes, recognised by the 1982 Nobel Prize in Physiology or Medicine. The central question is: How do ATP, calcium, and membrane interactions determine which regulatory states of human 5-lipoxygenase (5-LOX) can be targeted using new modulators? Our ATP-bound cryo-EM structure, biochemical mutants, and molecular dynamics provide an experimental foundation, but the coupling between nucleotide recognition, membrane association, and allosteric control remains unresolved. We will integrate GPU-accelerated cryo-EM processing, replicated atomistic molecular dynamics simulations, quantum chemistry, machine learning, and genetic-algorithm/discrete molecular dynamics (GA/DMD) screening to resolve this mechanism. Cryo-EM classification and refinement will identify experimentally supported structural differences, and they will provide multiple PDB structures as input for molecular dynamics simulations; GROMACS, Psi4, and OpenMM will test their dependence on ATP occupancy, Ca2+ coordination, mutations, and lipid composition. Our GA/DMD framework will prioritize regulatory mutations for atomistic validation, while Psi4/SAPT will explain selected molecular interactions and iron-binding pocket interactions. Machine learning and deep learning will support conformational analysis and prioritization, where independent validation demonstrates added value.