"One of the great challenges is to understand how cellular functions emerge in cell membrane systems. Unlocking this mystery is the key to the vast majority of human diseases. The current view is based on a static picture where membrane proteins in protein-poor membranes interact with a few specific lipids, while in reality the situation is much more complicated. This ambitious project aims for a breakthrough by changing the present paradigm. The objective is to focus on the dynamical interplay between lipids and proteins under crowded conditions, paving the way for understanding the dynamics of lipid-protein complexes and their resulting functions. The objectives are outstanding and contain a high risk, with exceptional gain. The main goal is better understanding of the physical principles that give rise to cellular functions, with a strong impact to clarify the relevance of dynamical lipid-protein interactions in cellular processes related to health and disease. For this purpose, the grand themes chosen for this project are lipoproteins coupled to cardiovascular disease (“good” and “bad” cholesterol) and the function of especially cholesterol and glycolipids with membrane proteins. In order to meet these goals, the applicant employs state-of-the-art simulation techniques that comprise quantum-mechanical, classical atomistic and coarse-grained simulation methods to elucidate the complex biological phenomena associated with lipid-protein systems. The simulations cover atomistic and molecular details, over time scales from femtoseconds up to milliseconds. The theory & simulation group lead by PI comprises expertise in a truly cross- and multi-disciplinary manner, and it strongly collaborates with some of the leading experimental teams in biomedical sciences, cell biology, structural biology, and membrane biophysics."