To determine how membrane proteins are regulated is a new frontier in structural biology. We focus on proteins that transport metal ions across different types of biological membranes, which are regulated by lipid composition, pH, and internal domains. We use MD simulations to refine time-resolved X-ray solution scattering data using an approach that we have developed (Ravishankar et al., Science Advances, 2020 ; Orädd et al., Science Advances, 2021 ; Prabudiansyah et al, Science Advances, 2024). We have obtained X-ray data for both bacterial and human calcium-transporting transport proteins and now propose to use our MD-based refinement protocol for structural interpretation. We will simulate the proteins in detergent and also inserted into nanodiscs with differing lipid composition (that match the experimental conditions). The results will contribute to understanding fundamental membrane protein regulatory mechanisms and will be of high medical relevance since the protein targets are either involved in heart disease or constitute novel targets for developing new antibiotics.