Hello, A new project on the LCRC cluster has been requested. Please forward the information on to the LCRC Allocation sub-committee. Applicant's name: Ursula Perez Salas Applicant's institution: ANL Applicant's division: MSD Project Name: lipidmovement Project title: Curvature Effect on the Movement of Lipids Within and Between Membranes Associated funding: LDRD Other Systems: UIC extreme cluster Science: This project uses Molecular Dynamics simulations to investigate the diffusion of lipids, specifically DMPC and cholesterol, in curved lipid membranes. We will calculate the free energy profile of extraction as well as flip-flop in a curved lipid membrane, i.e. a vesicle. The results will be compared to those obtained from MD simulations on planar membranes, which agree with experimental data of planar membranes but disagree substantially from data on highly curved lipid vesicles. The curvature is expected to affect the transfer rate of lipids into the membrane as well as its movement across lipid leaflets. The results will provide an atomic-level explanation for different kinetic rates obtained in small angle neutron scattering experiments. The movement of lipids within membranes (flip-flop) together with the exchange between membranes under physiological conditions allows the creation of asymmetric distributions of lipids across cellular membranes. Further, the location of lipids and their rate of exchange have important biological consequences, especially for lipids involved in cellular signaling. Therefore decoding the underlying mechanisms that control lipid transfer between and within lipid membranes is critical for understanding lipid homeostasis in the cell as well as the metabolic pathways that sustain it. The proposed research seeks to identify key physical membrane properties, specifically curvature, which govern both exchange and flip-flop of lipids in membranes. Project description: We will use a coarse-grained description of the system using the MARTINI force field to create lipid vesicles of various diameters solvated in water. Cholesterol will be added to the system at extremely low and high concentrations, which will then partition into the lipid vesicle. A vesicle of 30 nm diameter results in a system of approximately 1M particles. The free energy profile across bilayer for a lipid is then calculated using the umbrella sampling technique. In this technique the phase space is divided into many small regions, which are sampled independently and then combined using the Weighted Histogram Analysis method to provide a single energy profile. In addition to the free energy profiles, long simulations will be run in order to directly observe the lipid movement. We will use the molecular dynamics program NAMD, which is developed at University of Illinois at Urbana-Champaign and is freely available for download (http://www.ks.uiuc.edu/Research/namd/). NAMD is highly parallel and scales efficiently with the number of particles in the system. Preliminary simulations of the system at the UIC cluster has shown a benchmark of 130ms/timestep on 64 cores. Using a time step of 20fs, we estimate that the proposed calculations require approximately 4 microseconds of simulation requiring a total of 460,000 core-hours. Project URL: Requested allocation: 460000 Q1: 115000 Q2: 115000 Q3: 115000 Q4: 115000 Justification: The requester has used undetermined amount hours of their initial startup project. In addition to approving an initial amount, please specify a Category and Subcategory for this project. For a list of the current selection of approved categories, please see: https://wiki.lcrc.anl.gov/wiki/Processes/Categories Once the Allocation committee has approved the project, please go to the Project Management page to create it: https://accounts.lcrc.anl.gov/projects.php Thank You, The LCRC Accounts System